Six healthy subjects (two female) aged 23-40 years participated in a double-blind randomized cross-over study to investigate autonomic mechanisms involved in the chronotropic effect of adenosine in conscious man. Adenosine was infused in increasing doses following saline, propranolol (0.2 mg kg-1 body weight) or propranolol (0.2 mg kg-1 plus atropine (0.04 mg kg-1). Heart rate and blood pressure were measured supine, on standing and during a Valsalva manoeuvre. Plasma catecholamines were measured in the supine and standing positions. Following saline, adenosine (up to 120 micrograms kg-1 min-1) caused a dose-related increase in heart rate (mean +/- SD maximum increase 18 +/- 8 bpm; P less than 0.01). The change in heart rate with adenosine after propranolol (12 +/- 9 bpm; P less than 0.05) did not differ significantly from the corresponding change following saline but was abolished by propranolol plus atropine, which, in turn, was associated with a mean maximum decrease in heart rate of 5 +/- 3 bpm (P less than 0.01). The increase in heart rate during the initial 30 s on standing was augmented with adenosine compared with saline (16 +/- 5 bpm; P less than 0.01). A significant increase in plasma noradrenaline on standing was also found with adenosine compared with saline (6.37 +/- 2.86 vs. 4.77 +/- 1.79 nmol 1(-1); P less than 0.05). The heart rate response to the Valsalva manoeuvre was not affected by adenosine. These results suggest that the positive chronotropic effect of infused adenosine in conscious man may in part be caused by an inhibition of cardiac vagal tone.(ABSTRACT TRUNCATED AT 250 WORDS)