1. The mechanisms underlying the pronounced transient fall in arterial blood pressure evoked by a 3 s bout of bicycle exercise were investigated in twenty healthy young adults and four patients with hypoadrenergic orthostatic hypotension. 2. In healthy subjects a 3 s bout of upright cycling induced a 28 +/- 3 mmHg fall in mean arterial pressure at 12 s. The fall in mean arterial pressure was preceded by a 12 +/- 2 mmHg rise in right atrial pressure at 3 s and accompanied by a 54 +/- 7% increase in left ventricle stroke volume at 6 s. Systemic vascular resistance dropped 48 +/- 2% at 7 s after the start of the manoeuvre to remain at that level for approximately 5 s. The total response lasted about 20 s. During sustained upright cycling the initial fall in mean arterial pressure was also present, but less pronounced (17 +/- 2 vs. 26 +/- 3 mmHg). A 3 s bout of supine cycling in four patients with hypoadrenergic orthostatic hypotension also elicited a pronounced fall in mean arterial pressure (22 +/- 4 mmHg) and in systemic vascular resistance (38 +/- 4%). 3. A bout of exercise with a large muscle mass induces two main effects. First, it mechanically increases filling of the heart due to activation of the muscle pump, resulting in an increase in cardiac output. Second, it induces a drop in systemic vascular resistance. The increase in cardiac output is not sufficient to compensate fully for the pronounced fall in systemic vascular resistance and the result is a transient fall in arterial pressure at the onset of whole-body exercise. The rise in right atrial pressure evoked by 3 s cycling is abrupt and large, but the almost immediate onset and rapid fall of the systemic vascular resistance is too fast for sympathetically mediated reflex effects due to stimulation of the cardiopulmonary afferents. An important factor involved in the drop in systemic vascular resistance appears to be local, non-autonomically mediated vasodilatation in exercising muscles, since it also occurs in patients with autonomic failure.