In an experimental study increasing amounts of lysolecithin have been added to aliquots of plasma from 18 patients with a high erythrocyte sedimentation rate (ESR) and the final concentration of lysolecithin in the samples has been determined by means of thin layer chromatography and subsequent phosphorus determination as well as determination of the ESR. It was found that the ESR remained high in the different plasma samples until a critical level of lysolecithin was reached, whereafter the ESR abruptly dropped to lower values. This change took place within a very narrow concentration range, usually between 4.5 and 5.5 ,ug lysolecithin P/ml, and at a concentration of 7-8 pg/ml the ESR was consistently very low. In additional experiments, using decreasing amounts of red cells to the various plasma samples, the ESR had a normal tendency to increase inversely to the hematocrit, but in this case no threshold level could be observed. These findings clearly demonstrate that the lysolecithin concentration is of considerable importance for the ESR value. A low lysolecithin content of the plasma means a higher ESR value than expected from the amount of protein components, and a high lysolecithin concentration means a low ESR in spite of an unchanged protein pattern. Normally a decrease of the ESR takes place on incubation of a plasma sample due to the enzymatic formation of lysolecithin from lecithin. This phenomenon is explained by an increase of the lysolecithin amount above the demonstrated critical level. In a number of pathological conditions this "heat-stabilization" process does not occur, and in these cases the lysolecithin concentration is characteristically low and does not rise above the critical level even after incubation. A number of possible explanations of this drastical decrease of the ESR at a certain lysolecithin level are discussed in this presentation, but the most likely is that lysolecithin is bound to plasma proteins, e.g. albumin. In this form it is unable to exert its physiological effect on the red cell surface membranes until the saturation limit of the carrier protein is reached and "free" lysolecithin appears.Since Fkhraeus (9) described the sedimentation of red cells in plasma in 1921, an enormous num-ber of papers have dealt with factors affecting the erythrocyte sedimentation rate (ESR) and especially the plasma constituents enhancing this phenomenon. Fihraeus stressed in the first place the importance of fibrinogen and globulin fractions in this context. He maintained that in acute febrile or inflammatory states the increased ESR could be referred to a raised plasma fibrinogen concentration ("acute ESR increase"), whereas a globulin increase was generally found in morbid conditions of a chronic type ("chronic ESR increase").In his work Fihrsus was also able to show that incubation at body temperature of a plasma with a high ESR caused a considerable reduction of the ESR compared with the basal value of a non-incubated plasma sample. In collaboration with Bergenhem (1) he later discussed ...