The endocochlear potential (EP), and the concentration of K+, Na+ and Cl- were measured simultaneously in endolymph of guinea pigs. The EP was 85.6 +/- 0.8 mV in normal guinea pigs, 90.7 +/- 0.8 mV in the kanamycin-treated animals, and 91.6 +/- 1.2 mV in those treated with nitrogen mustard-N-oxide (NMNO). Thirty minutes after the onset of anoxia, the EP (negative EP) was -29.3 +/- 1.0 mV in the normal group, -0.2 +/- 1.0 mV in the kanamycin-treated group, and -1.9 +/- 1.3 mV in the NMNO-treated group. The permeability coefficients of K+ (Pk), Na+ (Pna) and Cl- (Pcl) across the endolymph-perilymph barrier during the period of 20-30 min after the onset of anoxia in the normal group were (341.6 +/- 38.2) x 10(-9) cm3 sec-1, (53.0 +/- 8.1) x 10(-9) cm3 sec-1 and (111.8 +/- 27.2) x 10(-9) cm3 sec-1, respectively. Pk was decreased in the kanamycin- and NMNO-treated groups. Pna did not differ between the normal and treated groups. Pcl was increased in the kanamycin- and NMNO-treated groups. The K+:Na+:Cl- permeability ratio was 1:0.16:0.32 in the normal group, 1:1.12:11.6 in the kanamycin-treated group, and 1:0.44:5.60 in the NMNO-treated group. The results indicate that the lack of development of a negative EP in the kanamycin- and NMNO-treated guinea pigs was attributable to the increased Pcl and the decreased Pk across the endolymph-perilymph barrier, probably the organ of Corti, during anoxia.