Sera from foetal calves, newborn calves, athymic mice, and healthy postmenopausal women exert a growth inhibitory effect on the oestrogen receptor positive human breast cancer cell line MCF-7. This inhibitory effect of serum can be abrogated by oestradiol. Serum samples from 22 breast cancer patients were analysed for the amount of inhibitory activity in order to clarify whether regulation of cell proliferation of human breast cancer may occur via a modulation of the inhibitory activity in the patient's serum. Twenty of the 22 serum samples showed inhibitory activity and no difference was found in the degree of inhibition. These results do not support the hypothesis that breast cancer cells grow in vivo solely as a function of a reduced level of a serum-borne inhibitory activity; other mechanisms must be involved in the regulation of growth. We have found that MCF-7 cells, the growth of which is inhibited by serum from breast cancer patients, exhibit a reduced synthesis of three secreted proteins, and an increased amount of one protein, a 46K protein. Oestradiol induced cell proliferation is concomitant with stimulation of the synthesis of these three proteins and inhibition of the 46K protein. Regulation of growth of breast cancer may therefore occur via changes in the synthesis of secreted proteins, which exert a regulatory function on cell proliferation.