The histamine H-2 receptor antagonist cimetidine was given for 90 minutes to four fistula dogs during a steady dose 270-minute infusion of histamine (50 microgram. base/kg.hr.), urecholine (80 microgram./kg.hr.) or pentagastrin (1.5 microgram./kg.hr). In each case there was gradual but marked (75-95%) inhibition of acid secretion with maximal effects after 60-90 minutes while pepsin secretion was also suppressed but to a lesser extent. These effects persisted for at least the 90 minutes after the end of cimetidine infusion. Serum gastrin was not significantly changed by cimetidine. Kinetics of effect of cimetidine were derived from stepdose responses to histamine (2-150 microgram./kg.hr.), pentagastrin (0.1 to 10 microgram.kg.hr.) and urecholine 20-160 microgram./kg.hr.) which were made alone and with background infusions of cimetidine. Cimetidine acted competitively for acid output with histamine as the stimulus and noncompetitively for pentagastrin or urecholine. With histamine or pentagastrin pepsin was less inhibited than H+ and in the case of urecholine, pepsin secretion was not inhibited by cimetidine.