In sedentary individuals, H₁-receptors mediate the early portion of postexercise skeletal muscle hyperemia while H₂- receptors mediate the later portion. It is not known if postexercise hyperemia also presents in endurance trained individuals. We hypothesized that the postexercise skeletal muscle hyperemia would also exist in endurance trained individuals and that combined blockade of H₁- and H₂-receptors would abolish the long-lasting postexercise hyperemia in trained and sedentary individuals. We studied 28 sedentary and endurance trained men and women before and through 90 min after a 60 min bout of cycling at 60% V_O2peak on control and combined H₁- and H₂-receptor antagonist days (fexofenadine and ranitidine). We measured arterial pressure (brachial auscultation) and femoral blood flow (Doppler ultrasound). On the control day, femoral vascular conductance (calculated as flow/pressure) was elevated in all groups sixty minutes after exercise (sedentary men: 86 ± 35; trained men: 65 ± 18; sedentary women: 61 ± 19; trained women: 59 ± 23%: all P < 0.05 vs preexercise). In contrast, on the histamine antagonist day, femoral vascular conductance was not elevated in any of the groups after exercise (sedentary men: 21 ± 17; trained men: 9 ± 5; sedentary women: 19 ± 4; trained women: 11 ± 11%; all P > 0.16 vs preexercise; all P < 0.05 vs control day). These data suggest postexercise skeletal muscle hyperemia exists in endurance trained men and women. Furthermore, histaminergic mechanisms produce the long-lasting hyperemia in sedentary and endurance trained individuals.