Sudden, severe thrombocytopenia developed in each of three patients receiving diphenylhydantion, diazepam, and sulfisoxazole, respectively. Recovery followed discontinuance of the drugs. An antiplatelet antibody requiring the presence of an appropriate drug for interaction with platelets was deomonstrated in each case by the 51Cr platelet lysis test using normal, paroxysmal nocturnal hemoglobinuric, or enzyme-treated normal platelets as target cells. These antibodies could not be detected by techniques that depend on clot retraction inhibition, complement fixation, or platelet factor-3 activation. Quinine-and quinidine-dependent antiplatelet antibodies in the serum of 16 patients who developed acute thrombocytopenia while taking either quinine or quinidine could be demonstrated readily with the 51Cr platelet lysis test and could also be detected by other methods employed.