Infection of cultured vertebrate cells by Sindbis virus, an alphavirus, results in a reduction in the overall rate of protein synthesis and in selective termination (shutoff) of host-specified protein synthesis. The shutoff of host protein synthesis by Sindbis virus has been temporally correlated with a decrease in intracellular K+ concentration (and an increase in intracellular Na+ concentration) which occurs as a consequence of virus-mediated inhibition of the plasma membrane-associated Na+/K+ ATPase. Incubation of Sindbis virus-infected cells in medium containing an elevated concentration of K+ resulted in an increase in the intracellular concentration of K+, an increase in the overall rate of protein synthesis, and in partial reversal of the virus-induced termination of cell-specified protein synthesis. These results suggest that the virus-induced decrease in intracellular K+ concentration is required for efficient shutoff of host protein synthesis by Sindbis virus.