A highly leukemogenic virus (DMBA-LV) induces thymic lymphomas with a very short (40 days) latent period. All induced tumors contain low numbers of new integrated DMBA-LV type-B proviruses and tumorigenicity of DMBA-LV is completely abolished by a monoclonal antibody directed toward an envelope determinant present on a type-B mammary tumor-inducing viral isolate. While the DMBA-LV type-B genome is very highly related to mammary tumor-inducing isolates it does have unique gp52 and p28 proteins as well as unique restriction endonuclease sites. In the present study the target cell specificity of DMBA-LV was contrasted with that of the mammary tumor-inducing isolate MMTV (C3H). The results indicated that infection of CFW/D mice with DMBA-LV could be detected in the thymus only as early as 17 days postinfection and by 40 days postinfection all 40 thymuses examined contained new integrated proviral copies of DMBA-LV. In contrast, when mice were injected intrathymically with MMTV (C3H) virus infection was transiently detected in the thymus only at 28 days postinfection. By 35 and 42 days postinfection there was no indication that virus-infected cells were still present. Analysis of individual thymic lobes following DMBA-LV infection suggested that independent tumors may be initiated in each of the separate lobes. Furthermore, there appeared to be a correlation between the weight of the lobe and the number of new DMBA-LV proviral copies, the larger the lobe the greater the number of newly integrated proviral copies.