Na-K changes and cytotoxic effects were monitored in HeLa cells infected with encephalomyocarditis (EMC) virus, human rhinovirus or vesicular stomatitis virus (VSV). Whereas in all three cases Na-K changes followed viral inhibition of cellular protein synthesis, such changes preceded trypan blue staining of rhinovirus-infected or VSV-infected cells and paralleled trypan blue staining of EMC virus-infected cells. In each case a progressive reduction in cellular electrical volume was associated with Na-K changes. K leakage from EMC virus- or rhinovirus-infected cells clearly exceeded Na gain by these cells. These findings are basically similar to those previously reported for poliovirus-infected HeLa cells. It is concluded that Na-K changes induced by picornaviruses or VSV do not trigger shut-off of HeLa cell protein synthesis, but may contribute to late manifestations of cytotoxicity.