Female Swiss mice susceptible to skin tumors received 6 sc injections and/or topical applications of dehydroretronecine, a metabolite of the pyrrolizidine alkaloid monocrotaline, and were observed for 15 months for tumor development. Of 92 animals examined, 63 had tumors at the site of application or injection; 47 of these had skin tumors, mainly basal cell and squamous cell carcinomas. These data indicate that dehydroretronecine is a proximate carcinogen capable of causing a high incidence of skin tumors in mice at the site of sc injection or topical application.