In a prospective study, 16 of 52 patients treated with conventional doses of beef lung heparin developed thrombocytopenia (platelet counts less than 100 × 10 9/l). Plasmas available from eight of these 16 patients failed to aggregate platelets from normal donors in the presence of heparin. Of five patients tested, plasma obtained from one patient during heparin therapy caused increased serotonin release when compared to plasma obtained before heparin therapy. Plasma from four other patients did not show increased serotonin release. Complement fixation studies were negative in these five patients. The essentially negative tests for heparin-dependent antibody formation suggest that frequently the etiology of the heparin-associated thrombocytopenia may not be immunologic.