In heartworm-infected dogs, circulating filarial factors appear to be responsible for the seasonal depression of endothelium-dependent responses seen in the in vivo femoral artery. The effect of heartworm infection on vascular responses of the femoral artery in vitro, when the vessel is not constantly exposed to circulating factors, is unknown. Experiments were designed to test the hypothesis that in vivo exposure to circulating filarial factors leads to changes in the magnitude and mechanism of endothelium-dependent relaxation that are demonstrable in vitro. Rings of femoral artery from heartworm-infected and noninfected control dogs were suspended in muscle baths, and dose-response relationships to endothelium-dependent (methacholine) and -independent (sodium nitroprusside) vasodilators were done. To determine the mechanism of relaxation, dose-response relationships were also done in the presence of an inhibitor of nitric oxide synthase (L-NAME), an inhibitor of guanylate cyclase (methylene blue), or an inhibitor of cyclooxygenase (mefenamic acid). Heartworm infection did not depress endothelium-dependent relaxation of the femoral artery in vitro. Furthermore, the mechanism of relaxation in heartworm and control femoral artery is identical. These data suggest that the effect of circulating filarial factors that alter the magnitude and mechanism of relaxation in systemic vessels in heartworm-infected dogs rapidly disappears in their absence. This results has important bearing on the dynamics of heartworm-induced pathophysiological changes during infection and could influence the nature and chronology of responses to therapy.