Combined use of cimetidine and phenytoin among 1512 neurosurgical patients has led to severe thrombocytopenia in 4 patients. One died, and 1 became vegetative. We propose that cimetidine and phenytoin act synergistically to depress the megakaryocyte at the bone marrow. Because thrombocytopenia and inadequate hemostasis are hazardous in neurosurgery, we recommend discontinuation of the cimetidine and phenytoin combination.