Microbial infection causes inflammation which stimulates macrophage functions. One of the inflammatory products, lysophosphatidylcholine (lyso-Pc), can stimulate macrophage activities. Treatment of mice with lyso-Pc enhanced spreading and ingestion activities of peritoneal macrophages. In vitro treatment of macrophages with lyso-Pc greatly enhanced spreading but not ingestion activities. However, incubation of a mixture of adherent and nonadherent cells with lyso-Pc produced a markedly enhanced ingestion activity of macrophages, implying the contribution of nonadherent cells to the stimulation of macrophages. Time course studies of the stimulation of these macrophages showed that spreading activity is stimulated immediately, even 30 min, after their contact with lyso-Pc while induction of ingestion activity requires a latent period of about 5 h. When the specificity of the macrophage receptors for ingestion was analyzed using defined immunoglobulins (i.e., IgG and IgM) with or without complement, lyso-Pc-activated macrophages efficiently ingested IgG-coated sheep erythrocytes independent of complement. However, macrophages of the same lyso-Pc-treated mice did not ingest erythrocytes coated with IgM and complement. These observations suggest that lyso-Pc-stimulated macrophages ingest the targets via Fc-receptors but not C3b receptors.