Intrathymic injection of SMX-1, a dualtropic murine leukemia virus (MuLV) originally derived from Moloney murine leukemia virus stocks, protects AKR mice from developing MuLV-accelerated leukemia and spontaneous leukemia. Thymuses of SMX-1-injected mice show no change in weight, morphology, or thymocyte size, and quantitative expression of Thy-1 and Lyt-2 differentiation antigens is identical to control mice. The amplified thymic expression of MuLV-related antigens that occurs spontaneously in 6-month-old preleukemic AKR mice or that can be induced in young AKR mice by leukemogenic AKR dualtropic MuLV is prevented by SMX-1. It appears unlikely that the protective effect of SMX-1 is explicable in terms of cross-immunogenicity with transforming MuLV or transformed cells. As SMX-1 persists for long periods after intrathymic injection and does not alter levels of thymic ecotropic MuLV, SMX-1 may interfere with the generation, spread, or leukemogenicity of dualtropic MuLV that form de novo in AKR thymus during the late preleukemic phase. SMX-1 provides a way to probe the events leading to cell transformation in AKR mice.