Cadmium is an environmental contaminant that is both a human toxicant and carcinogen. To inhibit cadmium-induced damage, cells respond by increasing the expression of genes that encode stress-response proteins. We previously reported the identification of 48 cadmium-inducible mRNAs in the nematode Caenorhabditis elegans. Here we describe a new cadmium-responsive gene, designated cdr-1, whose rate and level of inducible expression parallel those of the C. elegans metallothioneins. The CDR-1 mRNA contains an open reading frame of 831 bp and encodes a predicted 32-kDa, integral membrane protein. Following cadmium exposure, cdr-1 is transcribed exclusively in intestinal cells of post-embryonic C. elegans. In vivo, the CDR-1 protein is targeted specifically to the intestinal cell lysosomes. cdr-1 transcription is significantly induced by cadmium but not by other tested stressors. These results indicate that cdr-1 expression is regulated by cadmium and in a cell-specific fashion. Inhibition of CDR-1 expression renders C. elegans susceptible to cadmium toxicity. In conclusion, cdr-1 defines a new class of cadmium-inducible genes and encodes an integral membrane, lysosomal protein. This protein functions to protect against cadmium toxicity.