Atropine sulfate causes bradycardia in doses which are greater than the usual anticholinergic doses producing tachycardia (Shucard and Andrew, 1977, Res. Comm. Chem. Path. Pharmacol. 16, 401-410). The present study was designed to evaluate the effects of large doses of atropine sulfate on heart rate and systemic blood pressure in rats. Six groups of urethane anesthetized, male, Sprague Dawley rats (200-450 g) were injected with varying doses of atropine via the jugular vein. Groups I through IV received 5 mg/kg, 20 mg/kg, 40mg/kg and 80 mg/kg, respectively. Group V was bilaterally vagotomized before the injection of 80 mg/kg of atropine. Animals in Group VI were bilaterally vagotomized and pretreated with propranolol-HCl before injection of 40 mg/kg of atropine. Atropine caused a significant (p less than 0.005) dose-dependent reduction in both heart rate and blood pressure. The negative chronotropic property of atropine shown in these experiments is in agreement with recent in vitro and in vitro studies. The cause of bradycardia in these doses appears to be an intrinsic property of atropine rather than being centrally mediated. Possible direct action by atropine on peripheral vascular resistance is discussed.