Experiments were performed to investigate, in the normal and acutely inflamed rabbit knee joint, the role of prostaglandins in the regulation of joint blood flow, measured by laser Doppler flowmetry, as well as their modulation of sympathetic vasoconstriction. Close intra-arterial injection of prostaglandin E(2) (PGE(2)) produced a dose-dependent vasodilatation in control joints, but the responses in inflamed joints were much smaller. Close intra-arterial infusion of indomethacin significantly increased the responses of the control joints to PGE(2), but had no effect on the responsiveness of the inflamed joints. Nerve-mediated vasoconstrictor responses did not change significantly with close intra-arterial infusion of indomethacin, either in control or in inflamed joints. Indomethacin infusions decreased basal joint blood flow in the control joint significantly more than in the inflamed joint. The systemic blood pressure was elevated slightly only in the control group. The results of this study show that although prostaglandins have a role to play in regulation of basal blood flow in both normal and acutely inflamed rabbit knee joints, they do not appear to play a significant role in modulation of sympathetic vasoconstrictor responses. Prostaglandin E(2) receptors are functional in normal knee joint blood vessels, but they may be disabled by the process of inflammation.