Impaired parasympathetic control of heart rate is associated with increased incidence of cardiac dysrhythmias and ischemia. Anticholinergic drugs suppress parasympathetic control and could be detrimental in the early postoperative period in high-risk patients. In this double-blind randomized trial, 30 ASA physical status I and II patients undergoing minor surgery received either atropine 20 micrograms/kg and neostigmine 50 micrograms/kg (Group A), glycopyrrolate 8 micrograms/kg and neostigmine 50 micrograms/kg (Group G), or placebo (Group P) for reversal of neuromuscular blockade. Two indices of parasympathetic modulation of heart rate, spontaneous baroreflex sensitivity, and high-frequency heart rate variability, were assessed. At 2 h after reversal, Group A showed persisting impairment of baroreflex sensitivity with respect to Group P (7.12 +/- 0.86 vs 12.71 +/- 1.38 ms/mm Hg, P = 0.022) as well as decreased high-frequency heart rate variability (280.8 +/- 30.1 vs 569.2 +/- 115.2 ms2/Hz, P = 0.015). Groups A and G showed a borderline decrease in normalized high-frequency variability at 2 h (P = 0.05 for Groups A and G versus Group P). Anticholinergic drugs with neostigmine cause impairment of parasympathetic control of heart rate which persists into the early postoperative period. The effects of glycopyrrolate appear to be of shorter duration; this drug may thus be preferable in patients at risk of cardiovascular complications.