We investigated the antiproliferative effect of different concentrations (10, 100, 1000 IU/ml) of alpha-, beta- and gamma-interferons (IFN) on breast cancer cell lines. Cell lines were treated with IFN, in the absence or in the presence of estradiol for 9 days, and the effect on growth was evaluated as variation in DNA content. Inhibitory effect varied as a function of the type of interferon and cell line. Alpha-IFN and gamma-IFN were effective only at 1000 IU/ml and not in all cell lines, whereas a maximum effect was observed for beta-IFN regardless of the steroid receptor status of cell lines. In fact, a significant growth inhibition was observed at the intermediate concentration of 100 IU/ml in all but MDA-MB231 cell lines. Moreover, in both estrogen-receptor positive cell lines, beta-IFN counteracted growth stimulation induced by estradiol and showed a strong antiestrogenic activity. In conclusion, our results show that beta-IFN is the most active among the IFNs tested and suggest its usefulness in the treatment of all breast cancers, irrespective of their steroid receptor status.