1. The effects of millimolar concentrations of glutaraldehyde on the electrophysiological properties of the epithelium of frog skin (Rana temporaria) were investigated. We recorded short-circuit current (Isc), transepithelial conductance (Gt) and impedance (Zt), fractional resistance (fRo) and the potential difference across the apical membrane (Vo). We used either Na+ or K+ as major mucosal cations to compare the effects on transepithelial Na+ and K+ currents (INa and IK) and thus on the apical Na+ and K+ permeabilities. 2. At concentrations above 0.005% (w/v) or 0.5 mM, glutaraldehyde irreversibly and completely inhibits both INa and IK within 2-3 h. The initial time courses of the inhibition of transepithelial currents following serosal and mucosal applications of the compound markedly differ. 3. Glutaraldehyde decreased Gt in sulphate Ringer solutions while it augmented Gt severalfold in chloride Ringer solution. 4. Measurements of the transepithelial impedance of tissues incubated with sulphate solutions showed that glutaraldehyde increased the resistances of both apical and basolateral membranes significantly. The capacitance of the apical membrane was augmented, while the basolateral membrane capacitance was drastically decreased. 5. Microelectrode impalements of the granulosum cells showed that glutaraldehyde decreased Vo by more than 40 mV and increased fRo, which reached values around 90%. 6. The role of free amino groups in ion-transporting proteins and the potential non-fixative uses of protein cross-linkers in epithelia are discussed.