Cimetidine and ranitidine are used in patients with life-threatening gram-negative infections, endotoxemia and acute stress erosions. Disposition kinetics of cimetidine and ranitidine in endotoxin pretreated rats was investigated. The H2-antagonists were administered intravenously 24 h after endotoxin (10 mg/kg) pretreatment. This endotoxin dosage resulted in 50% mortality in rats. Blood samples (0.25 ml) were collected at different timed intervals. No significant differences were observed in plasma clearance, half-life and volume of distribution between endotoxin pretreated and control rats. Cimetidine is eliminated extensively by the renal route in animals and man with metabolism being a minor process. Ranitidine is metabolized to a large extent (70%) in rats, while in humans this represents a minor process. No significant changes in cimetidine and ranitidine disposition parameters in endotoxin pretreated rats were observed. These results suggest that cimetidine and ranitidine may be used in normal dosages in endotoxemia patients since their pharmacokinetic parameters would not be affected under these circumstances.