Effects of the vasodilator dipyridamole (Dip) on plasma adenosine levels, heart rate, blood pressure and skin microcirculation were studied in 13 healthy male volunteers. Venous plasma concentrations of adenosine, catecholamines, dipyridamole and theophylline were determined by HPLC. Skin capillary blood cell velocity (CBV) was measured by videophotometric capillaroscopy in the finger nailfold. The adenosine uptake inhibitor Dip (approximately 1-3 microM in plasma) increased plasma adenosine from 0.15 +/- 0.03 to 0.29 +/- 0.03 microM (p less than 0.01) and heart rate (HR) by 13 +/- 2 beats/min (p less than 0.01) and reduced diastolic blood pressure by 6 +/- 2 mmHg (p less than 0.05). Dip did not significantly affect the skin circulation since basal CBV, digital pulse amplitude (DAPA), skin temperature and post-occlusive reactive hyperemia were unchanged. Plasma catecholamine levels were also unaffected. The adenosine receptor antagonist theophylline (45-55 microM in plasma) did not influence basal plasma catecholamine or adenosine levels, HR, blood pressure or skin microcirculation. Following theophylline Dip caused similar elevations of plasma adenosine but no changes in HR or blood pressures. Our results support the hypotheses that Dip dilates blood vessels in man by elevating endogenous adenosine and that theophylline acts as an adenosine antagonist. Under basal conditions, the skin microcirculation appears to be regulated mainly by factors other than adenosine.