In normally active individuals, postexercise hypotension after a single bout of aerobic exercise is due to an unexplained peripheral vasodilatation. Histamine has been shown to be released during exercise and could contribute to postexercise vasodilatation via H1 receptors in the peripheral vasculature. The purpose of this study was to determine the potential contribution of an H1 receptor-mediated vasodilatation to postexercise hypotension. We studied 14 healthy normotensive men and women (ages 21.9 +/- 2.1 years) before and through to 90 min after a 60 min bout of cycling at 60% on randomized control and H1 receptor antagonist days (540 mg oral fexofenadine hydrochloride; Allegra). Arterial blood pressure (automated auscultation) and femoral blood flow (Doppler ultrasound) were measured in the supine position. Femoral vascular conductance was calculated as flow/pressure. Fexofenadine had no effect on pre-exercise femoral vascular conductance or mean arterial pressure (P > 0.5). At 30 min postexercise on the control day, femoral vascular conductance was increased (Delta+33.7 +/- 7.8%; P < 0.05 versus pre-exercise) while mean arterial pressure was reduced (Delta-6.5 +/- 1.6 mmHg; P < 0.05 versus pre-exercise). In contrast, at 30 min postexercise on the fexofenadine day, femoral vascular conductance was not elevated (Delta+10.7 +/- 9.8%; P = 0.7 versus pre-exercise) and mean arterial pressure was not reduced (Delta-1.7 +/- 1.2 mmHg; P = 0.2 versus pre-exercise). Thus, ingestion of an H1 receptor antagonist markedly reduces vasodilatation after exercise and blunts postexercise hypotension. These data suggest H1 receptor-mediated vasodilatation contributes to postexercise hypotension.