In xiphophorine fish suffering from a genetically caused melanoma, both suppression of melanoma development and regression of the existing melanoma were observed after treatment of the fish with an "anti-melanoma immune RNA." This RNA was extracted from the lymphoid organs of guinea pigs immunized with fish melanoma. RNA from guinea pigs immunized with fish skin or liver and RNA from nonimmunized guinea pigs were ineffective. RNase treatment of the anti-melanoma immune RNA diminished its activity, although Pronase treatment did not. Analysis of antisera obtained from guinea pigs and rabbits immunized with either melanoma or normal skin of xiphophorine fish revealed differences in the immune responses induced by these tissues. The anti-melanoma sera recognized antigens in melanoma extracts, which were not present in skin extracts. These antigens were not recognized by the anti-skin sera. The results suggest specificity of the anti-melanoma immune RNA.