Indium (In), gallium (Ga) and arsenic (As) are major components of III-V semiconductors. The binary compounds InAs and GaAs possess distinct advantages in electronic properties over silicon-based semiconductors, hence increased human exposure is expected. In, Ga, and As alone or in combination are known to exert toxic effects on various tissues. Previous studies in our laboratory have shown that marked alterations in protein synthesis patterns occur in hamster kidneys following in vivo exposure to As. Included in these changes is the induction of a 32-kDa stress protein thought to be heme oxygenase (HO-1). The objectives of this study were to establish the identity of this protein as HO-1 and test the hypotheses that 1) In and Ga may alter the effects of As in the kidney and 2) HO-1 is induced by damage from oxidative intermediates generated by the metal ions. Supernatants obtained from hamster kidney proximal cortical tubule cells exposed in vitro and from hamster kidneys exposed in vivo to In, Ga, and As alone and in combination were assayed for HO-1 by Western blot analysis. HO-1 was increased in both the in vitro and in vivo As, In and Ga exposed cells. In and Ga when administered with As did not alter the HO-1 response. The capacity of the metals individually and in combination to generate oxidative radicals was determined by carbon monoxide (CO) and thiobarbituric acid reactive substances (TBARS) measurements in an in vitro system. The three metals had little capacity to directly generate oxidative products. Furthermore, studies showed that In and Ga inhibited the production of CO and TBARS when added to an Fe+3/ascorbic acid free radical generating system. These studies indicate that 1) In and Ga do not alter the stress protein response of kidney cells exposed to As and 2) In, Ga and As induce HO-1 by other than the direct production of oxidative free radicals.