Amphotropic murine leukemia viruses (MuLV-A) cause mainly lymphoma in newborn inoculated NIH Swiss mice after a long latent period of 6-12 months. Rarely, however, about 1% of the inoculated mice develop hind limb paralysis and progressive central nervous system disease. The biological properties and RNase T1-resistant oligonucleotide fingerprints of the recovered viruses from tissues of both lymphomatous and paralyzed mice inoculated with MuLV-A were analyzed. These results indicate that serial in vivo passages of MuLV-A in NIH Swiss mice lead to generation of new MuLVs of both amphotropic and ecotropic host ranges. The recovered amphotropic viruses are highly lymphomagenic and are recombinants of MuLV-A-specific oligonucleotides and endogenous mouse sequences. The ecotropic viruses fall into two groups: (1) recombinants of MuLV-A genes and NIH Swiss mouse viral or cellular sequences and (2) new ecotropic viruses with oligonucleotide fingerprints not related to any of the known MuLVs. The naturally occurring ecotropic MuLVs of the wild mice produce both lymphoma and paralysis in NIH Swiss mice. The viruses recovered from in vivo passages are mainly of ecotropic host range although dual-tropic virus activity is occasionally seen in the spleens but not in the brains or spinal cords of the lymphomatous or paralyzed mice. Oligonucleotide fingerprinting of the recovered MuLV-Es from paralyzed mice are identical to the input MuLV-Es, indicating that the parental MuLV-E alone, without recombination, is responsible for the paralytic disease.