The effects of cimetidine or ranitidine pretreatment on the intestinal absorption, plasma and urine level of caffeine, gastric acidity of mouse, and sleeping time by hexobarbital sodium were investigated pharmacokinetically. Cimetidine and ranitidine pretreatments were found to increase both the rate and extent of absorption of caffeine in rats. Cimetidine pretreatment increased blood level of caffeine and decreased urine level, while ranitidine pretreatment had no effect on urine level of caffeine. Ranitidine pretreatment inhibited gastric secretion due to caffeine more than cimetidine pretreatment. Cimetidine pretreatment increased the action of caffeine and showed shorter sleeping time by hexobarbital sodium, comparing with ranitidine pretreatment.