This paper describes two cases of nafcillin-induced platelet dysfunction, with positive rechallenge data for one patient. Nafcillin resulted in abnormal bleeding times in both patients and a clinically apparent bleeding episode in one of the cases. Platelet function tests were performed on one patient during the initial therapy and after rechallenge with nafcillin. Platelet aggregation showed abnormal responses to ADP, collagen, and epinephrine. Platelet count and morphology were normal. Nafcillin should be recognized as another antibiotic which causes platelet function abnormalities and clinical bleeding episodes.