Rapid, transient expression of the c-fos proto-oncogene is induced by the beta-adrenergic agonist, isoproterenol, in vivo and by numerous factors promoting growth and differentiation in cultured cells. We wanted to determine whether cellular stressors, which are known to induce expression of the gene encoding the major heat shock protein, hsp 70, also induced expression of the c-fos gene. Our findings demonstrate that c-fos mRNA levels increase transiently under conditions of heat stress or sodium arsenite treatment which induce expression of hsp70 mRNA in cultured cell lines. When 3T3 cells are heat shocked in the presence of amiloride, an inhibitor of Na+/H+ exchange, the induction of c-fos mRNA is partially inhibited, whereas that of hsp70 is somewhat enhanced. However, neither response requires ongoing protein synthesis. In fact, dramatic superinduction of c-fos mRNA is observed in cells which are heat shocked in the presence of the protein synthesis inhibitor, anisomycin. A comparison of relative rates of protein synthesis and c-fos mRNA levels during either heat shock or sodium arsenite treatment suggests that the transient suppression of protein synthesis accompanying these treatments may be one factor responsible for the observed c-fos mRNA induction.