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The gp70s isolated from normal mouse tissues by radioimmune precipitation and SDS-polyacrylamide gel electrophoresis (SDS-PAGE) were shown to be highly pleomorphic. Their apparent molecular weights calculated from SDS-PAGE ranged from 75000 for thymus gp70 to 65000 for epididymal secretion gp70. Differences in the M r of tissue-associated gp70s were confirmed by double-label co-electrophoresis studies. In addition, a high degree of primary structural pleomorphism among tissue-associated gp70s was demonstrated using two-dimensional tryptic peptide fingerprint analysis. These studies showed that most of the conserved peptides of tissue-associated gp70s were also common to xenotropic murine leukaemia virus (MuLV) gp70s. Thus, tissue-associated gp70s are probably encoded by endogenous xenotropic MuLV env genes or gene fragments. Tissue-associated gp70s also showed a very high level of primary structural pleomorphism. These phenomena were observed for gp70s derived from the tissues of several strains of mice. Tissue-associated gp70 pleomorphism may arise as a consequence of at least two simultaneously operating mechanisms. First, the expression of pleomorphic forms of gp70s on murine tissues may be regulated by mechanisms that also determine the differentiated state of the tissues. Second, endogenous xenotropic env genes may be modified by recombinational or mutational events among these genes, or among cellular genes that regulate the expression of endogenous proviral genes.