Immunocytochemistry revealed an association between growth inhibition and a translocation of retinoblastoma protein (pRB) to the nucleoli of U-2 osteosarcoma cells inhibited in their growth by the negative growth factor NCPI (natural cell proliferation inhibitor). Similar phenomenon was demonstrated by Western blot analysis and immunocytochemistry in U937 leukemic cells inhibited in their growth and induced to differentiate by 12-O-tetradecanoylphorbol acetate (TPA). Total nuclear extract of control U937 cells gave an intense 110 KD band, while total nuclear extract of TPA treated cells produced an intense 60 KD band and a weak 110 KD band. No bands were observed for the purified nucleoli of control cells, but the purified nucleoli of TPA treated cells produced a 60 KD band. These results suggest that in the process of cell growth inhibition and differentiation, specific proteolysis of pRB and its translocation to the nucleolus may occur.