A sustained postexercise vasodilatation, which is histamine receptor mediated, has been observed following single bouts of whole-body exercise, but the mechanisms that regulate activation of histamine receptors following exercise are undefined. Exploration of vasodilatation after small muscle-mass dynamic or resistance exercise could provide novel insight into the pathways responsible for histamine receptor activation. We hypothesized that there would be a vasodilatation of the previously exercised limb following small muscle-mass dynamic and resistance exercise, which would be mediated by histamine receptors. We studied men and women before and after single-leg dynamic (n = 9) or resistance knee-extension exercise (n = 12) on control and blockade days (combined oral H(1) and H(2) receptor antagonism with fexofenadine and ranitidine). We measured arterial blood pressure (automated brachial oscillometry) and femoral artery blood flow (Doppler ultrasound). Dynamic exercise elevated leg vascular conductance in the active leg by 27.2 ± 8.4% at 60 min postexercise (P < 0.05 versus pre-exercise), but did not alter conductance in the rested leg (change, 4.6 ± 3.5%; P = 0.8 versus pre-exercise). The rise in conductance was abolished on the blockade day (change, 3.7 ± 5.1%; P = 0.8 versus pre-exercise, P = 0.2 versus control). Resistance exercise did not produce a sustained vasodilatation (change, -4.3 ± 4.7% at 60 min postexercise; P = 0.7 versus pre-exercise). These data indicate that histamine receptors are activated following dynamic, but not resistance, exercise. Furthermore, these data suggest that local factors associated with aerobic exercise, and not systemic factors or factors associated with high muscle force, are responsible for activation of histamine receptors in the previously exercised muscle.