The radiation leukemia virus (RadLV) is a chronic leukemia retrovirus that induces thymic lymphomas in C57BU6 mice after a latency of 3 to 6 months. During the pre-leukemic (PL) period, the number of thymic macrophages gradually increased up to 100 fold. Of the cells in a RadLV-induced lymphoma, 0.3% were large macrophages packed with infected lymphoma cells. These thymic lymphoma macrophages (TLM) also ingested RadLV-induced lymphoma cells in vitro. Cultured RadLV-induced lymphoma lines could activate and fix C3 fragments through the alternative complement pathway (ACP). C3-bound lymphoma cells elicited an oxidative burst (06) response in TLM but not in bone-marrow macrophages (BMM). However, 114 treatment of BMM rendered them capable of responding with an 0 6 following triggering by C3-opsonized cells. Thymic macrophages (TM) responded moderately with 0 6 to C3-opsonized cells and this response was elevated if the TMs were treated by rIL4. The OB reaction of the TLMs could be partially inhibited by anti-LFA-I or anti-MALA-2 antibodies, and was completely inhibited by anti-CR3 antibodies. These results suggest that 114 can prime macrophages for triggering an 0 8 reaction and that the interaction between C3-opsonized cells and ILCprimed macrophages is mediated primarily through CR3.