The effect of cimetidine on gallamine-induced neuromuscular paralysis was evaluated in urethane-anaesthetized and mechanically ventilated rats. 2. Intravenous cimetidine (between 3.2 and 100 mg/kg) produced an immediate and sustained potentiation of gallamine-induced neuromuscular paralysis. 3. Intravenous calcium (0.35 mmol/kg) completely reversed the cimetidine-induced potentiation of gallamine's effect. 4. Cimetidine alone did not produce neuromuscular paralysis. 5. Cimetidine did not alter either the serum concentration or the total serum clearance of gallamine. 6. Cimetidine thus potentiates the action of gallamine via a pharmacodynamic and not a pharmacokinetic mechanism.