The early (∼30 min) postexercise hypotension response after a session of aerobic exercise is due in part to H₁-receptor-mediated vasodilation. The purpose of this study was to determine the potential contribution of H₂-receptor-mediated vasodilation to postexercise hypotension. We studied 10 healthy normotensive men and women (ages 23.7 ± 3.4 yr) before and through 90 min after a 60-min bout of cycling at 60% peak O₂ uptake on randomized control and H₂-receptor antagonist days (300 mg oral ranitidine). Arterial pressure (automated auscultation), cardiac output (acetylene washin) and femoral blood flow (Doppler ultrasound) were measured. Vascular conductance was calculated as flow/mean arterial pressure. Sixty minutes postexercise on the control day, femoral (Δ62.3 ± 15.6%, where Δ is change; P < 0.01) and systemic (Δ13.8 ± 5.3%; P = 0.01) vascular conductances were increased, whereas mean arterial pressure was reduced (Δ−6.7 ± 1.1 mmHg; P < 0.01). Conversely, 60 min postexercise with ranitidine, femoral (Δ9.4 ± 9.2%; P = 0.34) and systemic (Δ−2.8 ± 4.8%; P = 0.35) vascular conductances were not elevated and mean arterial pressure was not reduced (Δ−2.2 ± 1.3 mmHg; P = 0.12). Furthermore, postexercise femoral and systemic vascular conductances were lower (P < 0.05) and mean arterial pressure was higher (P = 0.01) on the ranitidine day compared with control. Ingestion of ranitidine markedly reduces vasodilation after exercise and blunts postexercise hypotension, suggesting H₂-receptor-mediated vasodilation contributes to postexercise hypotension.