Abstract The involvement of central muscarinic receptors in mediating the Bezold-Jarisch reflex elicited by injection of 5-hydroxytryptamine (5-HT) was studied in urethane/chloralose-anesthetized rats. Intravenous bolus injection of 5-HT (3.1 to 50 μg/kg) evoked a short-lasting dose-related bradycardia and hypotension, the Bezold-Jarisch reflex, accompanied with bursts of the efferent cervical vagus nerve. Systemic administration of atropine (0.1 and 1 mg/kg) blocked not only the cardiac responses but also the efferent cervical vagus nerve activity changes. Although the afferent cervical vagus nerve was also activated by an intravenous bolus injection of 5-HT, these responses were not altered by the systemic administration of even a high dose of atropine (1 mg/kg). Intracerebroventricular (i.c.v.) administration of pirenzepine (1 and 10 μg/10 μ1), a selective M 1 receptor antagonist, caused a rightward shift of the 5-HT dose-response curve for efferent vagus nerve activity. In contrast, i.c.v. administration of muscarinic type 2 receptor antagonist, gallamine, and type 3 receptor antagonist, p-fluorohexahydrosiladifenidol, failed to alter the response in nerve activity to 5-HT. These results suggest that the activation of central nervous muscarinic receptors might be involved in mediating the Bezold-Jarisch reflex and that the subtype might belong to type 1.