The effect of natural beta-interferon (beta-IFN) on cell proliferation and steroid receptor level was investigated in CG-5 human breast cancer cell line. beta-interferon determines an appreciable diminution of cell growth, at concentrations ranging from 100 to 1000 IU/ml, which is enhanced when serum content of the culture medium is lowered. Low concentrations of beta-IFN (10-100 IU/ml) produce, after a 5-day treatment, an increase in estrogen receptors (ER) and progesterone receptors (PR). No variation of ER and PR levels is observed when beta-IFN is added directly to the cell homogenate before the assay. Our data suggest that beta-IFN could affect hormone sensitivity through a modification of ER and PR in neoplastic mammary cells.