An early, transient drop in peripheral blood platelets to a mean nadir value of 49% (range 31-83%) of the pretreatment value was seen in 31 patients during chemotherapy with cis-platinum, vinblastine and bleomycin (PVB). The mean number of platelets dropped by 22% during the first 24 h after the start of chemotherapy, nadir value was seen after 3 d, with recovery to 107% of pretreatment level on d 14-15. Platelet survival studies during PVB chemotherapy showed shortened platelet survival time and indicated increased destruction of platelets. Identical patterns of early, transient thrombocytopenia were seen in 6 patients treated with vinblastine only. The early fall in circulating platelets did not predict subsequent serious thrombocytopenia. There were no bleeding episodes in the 37 patients studied here, but the early thrombocytopenia seen after vinblastine therapy may possibly be of clinical importance in critically ill patients at risk for bleeding episodes. In rats, an early drop in circulating platelets occurred after a high dose of vinblastine, but not after bleomycin. Addition of bleomycin to vinblastine did not increase the vinblastine-induced thrombocytopenia. It is concluded that the early drop in peripheral blood platelets during chemotherapy with PVB is due to vinblastine.