Capsaicin, which causes release of neuropeptides including substance P, has been shown to cause dose-related increases in cochlear blood flow (CBF). Since CBF regulation is altered in animal models with endolymphatic hydrops, this study was designed to examine the effect of hydrops on capsaicin-induced CBF changes. CBF responses to 0.01 and 0.001% capsaicin applied to the round window membrane were measured in normal and 12-week hydropic guinea pigs using laser Doppler flowmetry. With 0.01% capsaicin, CBF increased by only 13 +/- 7.8% in the hydropic ear, compared with 34% +/- 13% in the normal animal (p = 0.027). With 0.001% capsaicin, CBF increased by only 7.5 +/- 4.2% in the hydropic ear, compared with 28 +/- 16% in the normal ear (p < 0.001). These findings demonstrate a reduced responsiveness to capsaicin with endolymphatic hydrops and suggest that hydrops causes an alteration in the peptidergic sensory fibers of the inner ear or in the vascular smooth muscle or both. The results are consistent with previous reports of reduced vascular responsiveness in hydropic guinea pigs and provide further evidence for abnormal CBF regulation in hydrops.