Central muscarinic receptors play an important role in the regulation of cardiac vagal nerve activity. We studied the inhibition of central muscarinic receptors and sympathetic nerve function in humans, since very little information is currently available on this subject. We examined the effects of graded doses of atropine (five doses, range 0.001 to 0.016 mg/kg) on heart rate, arterial pressure, heart rate variability, and muscle sympathetic nerve activity in 13 healthy young volunteers. Atropine caused biphasic effects on heart rate and the high-frequency (HF) power of R-R interval variability. At lower doses (< or =0.002 mg/kg for heart rate, 0.001 mg/kg for HF power), atropine decreased heart rate and increased HF power. In contrast, at higher doses, atropine increased heart rate and decreased HF power. Low-dose atropine significantly attenuated muscle sympathetic nerve activity, burst rate (bursts/min) by -30.5 +/- 6.0% and burst incidence (bursts/100 heart beats) by -23.8 +/- 6.9% at 0.002 mg/kg. Systolic and diastolic arterial pressure did not change with atropine infusion. Low-dose atropine (< or =0.002 mg/kg) did not significantly affect either low frequency (LF) power or LF/HF. These results suggest that central muscarinic receptors may modulate not only cardiac vagal nerve activity but also sympathetic nerve activity in the skeletal muscle vasculature.