The p15(E)-related polypeptides of radiation leukemia virus (RadLV)-derived viruses and of cells infected with prototype MuLV were analyzed by immunoprecipitation, SDS-PAGE, and immunofluorescence analyses. It was found that the p15(E)-related molecules of ecotropic and xenotropic viruses derived from RadLV lymphoma cell lines were distinguishable by reactivity with monoclonal anti-p15(E) antibodies and by SDS-PAGE profile. Ecotropic MuLV of RadLV origin encoded the p15(E)a antigen and produced a Pr15(E) of 20K MW. In contrast, xenotropic virus derived from RadLV did not express the p15(E)a antigen and by SDS-PAGE its Pr15(E) migrated at 21K. A previously undescribed, p15(E)-related molecule of 18.5K MW was associated with xenotropic RadLV. These differences were also reproduced by the prototype ecotropic, xenotropic, and dualtropic viruses.