As shown previously, tetrabutylhydroperoxide (t-BOOH) shrinks hepatocytes by release of cellular K(+). The hyperpolarization, the increase of K(+) selectivity, and the Ba(2+) sensitivity of K(+) release have been taken as evidence of activation of K(+) channels. To further define the ion channels involved, patch-clamp studies have been performed on rat hepatocytes. The data show that 0.1 mmol/l t-BOOH inhibits an inwardly rectifying K(+) channel and simultaneously activates a 35-pS K(+) channel. It is suggested that the activation of the latter channel population contributes to the observed K(+) release of hepatocytes following exposure to t-BOOH.