Random bred Syrian hamsters given s.c. injections of SV40 small t deletion mutants dl883, dl884, and dl890 rapidly develop reticulum cell sarcomas in the abdominal cavity in addition to slowly developing s.c. fibrosarcomas at the site of virus inoculation. Injection of wild type SV40 s.c. induces only fibrosarcomas at the site of inoculation. In an attempt to understand why mutations in the SV40 small t gene should lead to this difference in tumor-inducing capacity in hamsters, we studied cells from 12 abdominal reticulum cell sarcomas which were induced by the s.c. injection of SV40 mutants. Morphological and functional analyses indicate that these tumor cells are derived from MAC-2+ macrophages. They are highly granulated, vacuolated, and multinucleated, and they generally adhere to glass and plastic. In addition, they (a) phagocytose latex beads; (b) express high levels of class II major histocompatibility complex antigens; (c) contain beta-glucuronidase, acid phosphatase, and fluoride-inhibited nonspecific esterase; (d) contain lysozyme and fibronectin; and (e) express cell surface MAC-2 antigens. Thus, the small t deletions in the SV40 genome appear to permit the virus to transform cells that are distant from the site of virus inoculation; at this distant site, the cells transformed are of a specific lineage, MAC-2+ peritoneal macrophages. This specific tropism may reflect a unique characteristic of MAC-2+ cells or their precursors that renders these cells susceptible to SV40 mutants which are otherwise restricted in the range of cells that they can transform.