Previous data suggest that regulation of cochlear blood flow (CBF) may be abnormal in the hydropic guinea pig. The purpose of this study was to employ the technique of anterior inferior cerebellar artery (AICA) occlusion to measure CBF autoregulation in experimental endolymphatic hydrops. This study also addresses the role of the cochlear sympathetic neural innervation and nitric oxide in CBF regulation with hydrops. In anesthetized guinea pigs, CBF was measured with a laser Doppler flowmeter probe while the AICA was intermittently occluded with a microvascular occluder. The CBF response was measured in normal, 6-week, and 12-week chronically hydropic animals. The gain factors (0 = no autoregulation, 1 = complete autoregulation) for 1-min occlusion were 0.95 +/- 0.16 (control), 0.77 +/- 0.28 (6 week, P = 0.164), and 0.67 +/- 0.25 (12 week, P = 0.037). NG-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of nitric oxide synthase, was infused intravenously to assess basal nitric oxide (an endogenous vasodilator) production in the hydropic ear. With infusion of L-NAME, CBF was reduced by 9.16 +/- 11%, 10.7 +/- 10% (P = 0.87), and 16.6 +/- 18% (P = 0.95), in the control, 6-week, and 12-week animals, respectively. In a separate group of 12-week hydropic animals, the left superior cervical ganglion (SCG) was anesthetized with lidocaine, and AICA occlusions were performed pre- and post-blockade. Prior to blocking the SCG, the gain was 0.712 +/- 0.02 and afterwards 0.708 +/- 0.051 (P = 0.93). The above results show that there was a statistically significant reduction in CBF autoregulation in the 12-week hydropic animals. There was no difference in basal nitric oxide production in normal versus hydropic animals nor was there a change in autoregulation following blockade of the SCG. These data provide clear evidence for reduced CBF autoregulation in experimental endolymphatic hydrops.