Regulation of macrophage scavenger receptor (MSR) activity may be an important determinant of the extent of atherogenesis and the efficacy of host defense. The effect of M-CSF on this pathway was studied using a recently developed monoclonal antibody to murine MSR. M-CSF markedly and selectively increased MSR synthesis in murine macrophages (M phi); post-translationally the receptor appeared more stable and shifted to a predominantly surface distribution. Functionally M-CSF enhanced modified lipoprotein uptake and increased divalent cation-independent adhesion in vitro. These results suggest a plausible mechanism whereby M-CSF production in the atheromatous plaque microenvironment could promote the recruitment and retention of mononuclear phagocytes and subsequent foam cell formation. In addition, the Th1 cytokine (gamma-interferon) and Th2 cytokine (interleukin-4) had differential effects on MSR glycosylation in vitro suggesting a further possible regulatory role by these lymphokines on macrophage MSR function.