Summary. Neutrophil kinetics were studied in 17 patients with Felty's syndrome using an in vitro diisopropylfluorophosphate‐32P technique. Excessive margination of neutrophils was present in all patients, and was solely responsible for the neutro‐penia in 12. Five patients had a total blood neutrophil pool which was so low that they would have been neutropenic even with a normal ratio of marginated to circulating cells; in these the production rate was subnormal. In no case was neutropenia due to shortened nueutrophil survival. There was no correlation between either the degree of marrow cellularity, or serum lysozyme levels, and the measured neutrophil production rate. Two patients studied before and after splenectomy showed improvement in kinetic abnormalities following operation. We conclude that the principal mechanism responsible for the neutropenia in Felty's syndronie is excessive margination of cells. In about one third of patients neutrophil production is subnormal in addition, but excessive neutrophil destruction is an uncommon finding. Conventional laboratory investigations are of little or no help in defining the mechanism in an individual patient. The value of splenectomy still has to be established, although short‐term improvement in kinetic parameters may occur.

Thirteen cases of leukemia, 12 of them acute, occurred in 3 generations of a family comprising 293 members. Individual cases could not be linked to the possession of any of a range of genetic markers. Cytogenetic studies showed no constitutional chromosome abnormalities. Preliminary results of virologic studies suggested the presence of oncornaviruses in at least 1 leukemic individual in this family. This aggregation of leukemia cases likely resulted from a genetic, probably polygenic, predisposition, in association with the activity of leukemogenic factors whose nature remains to be clearly defined.

Normal non-adherent mononuclear cells were shown to inhibit colony formation by normal human marrow cells cultured for 7 d in semi-solid agar. Inhibition was the same using cells from the marrow donor or from an unrelated normal subject, and was shown to be dose-dependent over the range of 4 X 10(5) to 6 X 10(3) mononuclear cells per 1 X 10(5) marrow cells plated. Inhibition was not seen in 14 d cultures, and it is postulated that colony-forming cells sensitive to lymphocyte inhibition belonged to the population known to give rise to colonies after 7 d in culture. Cell fractionation studies showed that inhibition was due to non-B non-T lymphocytes, purified B cells or T cells being neither inhibitory nor stimulatory. Inhibition was only shown with intact viable lymphocytes and it was not possible to extract inhibitory activity from the cells, or to produce inhibition by media conditioned by lymphocytes. The effect was apparently due to a direct action on colony-forming cells in the marrow and was not due to inhibition of colony stimulating activity (CSA) production, or to absorption or inactivation of CSA. These results emphasize the need to include appropriate controls when looking for possible cell-mediated inhibitors in disease states, particularly when 7 d cultures are used.

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Mouse bone marrow forms colonies of granulocytes and monocytic phagocytes when cultured in the presence of human plasma, urine or "feeder layers" prepared from human leukocytes. By contrast, human marrow produces colonies i n the presence of leukocyte feeder layers but not in the presence of plasma or urine. It has been tacitly assumed that the response of mouse marrow to human blood leukocyte feeder layers is a measure of physiological substances released by those leukocytes which might control human granulopoiesis. This assumption however, has never been put to the test by comparing the response of mouse and human marrow to stimulation by leukocytes from the same individual. This has been done in the present study by using leukocytes from normal and leukemic subjects. Different human marrows responded similarly to stimulation by the same normal feeder layers, but there was no quantitative or qualitative correlation between the response of human and mouse marrows. Feeder layers from patients with acute granulocytic leukemia did not stimulate colony growth in normal human marrow but were as potent in stimulating mouse marrow colony growth as were feeder layers of normal leukocytes.We conclude that different factors may stimulate human and mouse marrows and that assays of granulopoietic factors of human origin should in future be carried out in human rather than mouse marrows.