In the current study we investigated the effect of two different doses of natural interferon-beta (IFN-beta) on steroid hormone receptors in 45 patients with advanced breast cancer. IFN-beta seems to regulate the receptor mechanisms, inducing in cutaneous metastases an increase of oestrogen and progesterone receptors. Moreover, using IFN-beta and tamoxifen as a combined therapy in 23 receptor-positive patients, no negative interference of the two drugs was observed and no relevant side-effects due to the treatment were noticed. The modulation of steroid receptor content by IFN-beta in advanced breast cancer might represent an interesting way to ameliorate the clinical responsiveness to anti-oestrogens.