CM-SM is a clonal line of human precursor mononuclear phagocytes inducible to macrophage differentiation in response to the tumor promoter phorbol ester 12-0-tetradecanoyl-phorbol-13-acetate (TPA). Untreated CM-SM cells contain single class, high-affinity (K, = 4.0 x 10' M) glucocorticoid-specific receptor sites (-60,000 per cell), as measured by a whole cell assay, at 37"C, using [JH]triamcinolone acetonide (TA). Exposure of CM-SM to dexamethasone (DEX) produced a progressive, dose-and time-related series of changes in CM-SM cell growth, saturation density, morphology, and functional properties, with half-maximal effects at about M for DEX. TA-receptor sites rapidly decreased (about 70%) after DEX treatment, witho u t any apparent change in steroid specificity and affinity. After 5 days in culture with a saturating concentration (3.6 x 10 M) of hormone, the cells reached a saturation density of about 9.0 x lob viable cellsiml (about 4.0 x lob viable cellsiml in the controls), while the modal volume of the resulting cell population was approximately 60%, as compared to the volume of untreated cells. DEX-treated cells appeared less differentiated than controls, as assessed by combined morphologic, antigenic, and cytoenzymatic analyses. DEX almost completely inhibited TPA activation of the following macrophage functions: adherency to t h e culture plate, expression of lysosomal enzymes, Fc and C, receptors, and stimulation of phagocytosis. After removal of DEX, the cells, within a few passages, returned to a state apparently identical to t h e untreated controls and could be induced to macrophage differentiation in response to TPA.