We isolated mutants of the nematode Caenorhabditis elegans resistant to 12-O-tetradecanoylphorbol-13-acetate (TPA). The TPA-resistant mutants, although they grew somewhat smaller than normal, reproduced well and behaved normally in TPA; they also did similarly in another phorbol ester tumor promoter, phorbol-12,13-didecanoate (PDD), thus proving they are also resistant to PDD. All the mutations defined by these TPA-resistant mutants were semidominant to the wild-type allele. The 15 independently isolated mutants all fell into the same complementation group, defining a single gene, tpa-1. The gene tpa-1 mapped near the marker gene dpy-9 on chromosome IV.