Nicotinamide, a specific inhibitor of poly(ADP-ribose) synthetase, was found to be a moderate inducer of hemoglobin synthesis in Friend erythroid leukemia cells (FLC). Therefore, the effect of other inducers, s-ch as dimethyl sulfoxide (DMSO), hexamethylene-bisacetamide (HMBA), and butyrate, on poly(ADP-ribose) synthesis was examined. The extent of poly(ADP-ribose) synthesis in nuclei of FLC treated with DMSO or HMBA began to decrease before many phenotypic changes including hemoglobin production and reached 30--50% of the level of nontreated control when the cells enter the stationary phase. FLC variants unresponsive to HMBA or DMSO did not exhibit as low an activity of poly(ADP-ribose) synthesis as their parent cells did by treatment with these inducers. In contrast, butyrate stimulated poly(ADP-ribose) synthesis transiently but distinctly (about 50%) at an early stage of culture (6--24 hr), but suppressed it at a later stage. Neither the cell growth nor degradation of poly(ADP-ribose) is correlated with the effect of inducers. These results suggest that the level of poly(ADP-ribose) synthesis is correlated with the differentiation of FLC.