We have examined the effects of vitamin D3 metabolites and retinoic acid on the myelomonocyte cell line U937. Inhibition of proliferation, measured by incorporation of 125iodo-deoxyuridine was seen at 72 h with 1,25-(OH)2D3 but not 25(OH)D3 or 24, 25(OH)2D3 metabolites. CD14 molecules, not normally present on U937 cells, were induced on the cell surface. However, Class II major histocompatibility complex (MHC) molecules were not induced and Class I MHC molecules not increased in density as determined by flow cytometry. Retinoic acid inhibited proliferation but failed to induce CD14 molecules. These data suggest that both 1,25(OH)2D3 and retinoic acid act as an antiproliferation signal to U937 cells; only 1,25-(OH)2D3 induces the differentiation towards a more mature phenotype.