Summary.-C3H and C57 BL/6 mice carrying methylcholanthrene-induced fibrosarcomas were injected i.p. daily with histamine, metiamide (anti-histamine type-2 receptor), histamine + metiamide, mepyramine (anti-histamine type-i receptor), serotonin and methysergide (anti-serotonin). Inhibition of tumour growth and lengthened survival were observed with histamine and histamine+ metiamide. The best results (both on tumour growth and survival) were obtained with serotonin. Survival was increased by metiamide and decreased by mepyramine and methysergide. In histamine-treated and in serotonin-treated mice, histological studies of the tumours showed large and numerous foci of haemorrhagic necrosis.Stimulation of histamine type-I or serotonin receptors and inhibition of histamine type-2 receptors play a beneficial role in the host's defence against tumours.

Summary.-Tissue histamine levels were studied in C3H and C57BL/6 mice bearing a methylcholanthrene-induced fibrosarcoma, in Wag rats bearing an aflatoxin B, -induced hepatoma, and in Commentry rats bearing a grafted hepatoma. Histamine levels were significantly higher (1-5 to 3 fold) in the tumour-bearing animals for ventral and dorsal skin, skeletal muscle and stomach fundus. Total histamine content was increased in the spleen.In C3H mice with McC3-1 fibrosarcoma, the excision of the tumour or its partial regression by intratumoral injections of Corynebacterium parvum induced a reversion to normal values.The tumour thus appears responsible for the increased histamine levels in tissues distant from the tumour.IN AN EARLIER STUDY, Lynch & Salomon (1 977a) compared the intensity of immediate hypersensitivity (anaphylactic type) reactions in normal C3H mice to those in mice carrying a 3-methylcholanthrene-induced fibrosarcoma (McC3). The intensity of active or passive anaphylactic shock decreased in the tumour-bearing mice. This was also the case for passive cutaneous anaphylaxis, the inhibition being strongest when the tumour was large. These results led us to investigate whether modifications of tissue histamine content could account for the diminished immediate hypersensitivity in tumourbearing mice. We had previously shown that, in many tissues (skin, skeletal muscle, stomach, kidney and blood) of C3H fibrosarcoma bearing-mice, the histamine levels were significantly higher than in normal mice (Scheinmann et al., 1979).The aim of the present work was to discover whether this apparently paradoxical increase in histamine levels in tissues distant from the tumour 1) could be found in other animals bearing other tumours, and 2) was dependent on the presence of the tumour. MATERIAL AND METHODS Animals and tumoursWag rats bearing a hepatoma.-Male rats (Wag strain) were fed from the time of weaning on a diet containing 250 ,ug/kg aflatoxin B1. Such a diet induces hepatomas in all rats and a small percentage of kidney tumours. In the present study, the animals were killed at 16 months and all of them were hepatoma-bearing. Ten males of the same breeding were used as controls.Commentry rats bearing a grafted hepatoma.-The LF hepatoma was a 4-dimethylaminoazobenzene-induced transplantable hepatoma. It was inoculated i.p. into 20-day old male rats of the same strain. The animals were killed 7-16 days after transplantation. Ten males of the same breeding were used as controls.C57BL/6 mice carrying a grafted fibrosarcoma.-The McB6-1 tumour is a fibrosarcoma induced by s.c. injection of 2 mg of 3-

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In comparison with those in normal (+/+) mice, tissue histamine levels were lower in athymic (nu/nu) female mice and higher in athymic male mice. The sexual difference was less marked or absent in nu/nu mice. These results show (a) that endocrine factors are involved in the distribution of tissue histamine, and (b) that the thymus cannot be considered as the main source of tissue histamine in pathogen-free mice.