Four groups of patients were examined serologically for hemagglutinating antipenicillin antibodies (HAPA). The incidence of HAPA was found to be 21.8 per cent in patients with rheumatoid arthritis or systemic lupus erythematosus, 37.8 per cent in patients treated with penicillin for syphilis, 7.9 per cent in patients with cardiovascular disease and 22.2 per cent in patients with penicillin allergies. These incidences were significantly higher than the 3.1 per cent frequency noted in healthy individuals donating blood in this survey.Although the reasons for the high incidences of HAPA vary for the patient groups, this study indicates that a substantial number of patients are at risk of developing positive direct antiglobulin reactions and/or acquired hemolytic anemias if treated with penicillin.