Lysophosphatidylcholine (lyso-PC), a product of inflammation, stimulates (in vivo) mouse peritoneal macrophages to ingest target cells via Fc receptors. In vitro treatment of macrophages with lyso-Pc was unable to enhance ingestion activity. When a mixture of macrophages and nonadherent (B and T) cells was treated with 20 micrograms of lyso-Pc/ml for 30 min, a greatly enhanced Fc-mediated ingestion was observed at about 3 hr after treatment, suggesting that nonadherent cells contributed to activation mechanism of macrophages. The accumulated evidence suggests that treated B cells collaborated with untreated T cells in a stepwise fashion for the exchange of a signaling factor(s) for macrophage activation. When conditioned medium prepared by stepwise cultivation from treated B cells to untreated T cells was used for cultivation of untreated macrophages, a markedly enhanced Fc-mediated ingestion was observed. However, cultivation of macrophages with stepwise conditioned medium of treated T cells and untreated B cells produced no significant enhancement of phagocytic activity. Therefore, we concluded that lyso-Pc-treated B cells initiated the macrophage activation process by releasing and transmitting a signaling factor to T cells, and, in turn, the T cells modified the factor or supplied a new factor capable of the ultimate activation of macrophages for ingestion capacity. This lyso-Pc-induced factor(s) appears to be distinct from the established interleukins 1 and 2.