Effects of testosterone (T) and estradiol-17beta (E-2) on the synthesis of DNA, RNA and protein were studied in explants of the following types of malignant and non-malignant human female breast grown in organ culture: cystic mastitis (7 cases), fibroadenoma (8), carcinoma (17) and uninvolved tissue from cancer-bearing breast (8). In cultures of systic mastitis T uniformly inhibited the incorporation of thymidine-3H into DNA, uridine-3H into RNA and L-amino acids-14C (AA-14C) into protein. E-2 inhibited the incorporation of thymidine-3H, but had a variable effect on the incorporation of uridine-3H and AA-14C. Cultures of fibroadenoma, with no steroid added, were highly proliferative especially at the outer surface, but the incorporation of thymidine-3H, uridine-3H and AA-14C was much lower than in cystic mastitis. Whereas in fibroadenoma T uniformly inhibited the synthesis of DNA, RNA and protein, the effect of E-2 was variable: in most cases it inhibited the synthesis of DNA,but in one it stimulated it appreciably; in the majority of cases E-2 stimulated RNA and protein synthesis. In cultures of cancerous tissue T depressed, in most cases, the incorporation of thymidine-3H, uridine-3H and AA-14C, but it stimulated it in 4 out of 17. E-2 inhibited the synthesis of DNA, RNA and protein in 6 cases (2 of them were inhibited by T), stimulated them in 9 (one stimulated by T) and had no clear effect in 2. The effect of the steroids on the explants of uninvolved tissue was variable and did not always parallel their effect on the cancerous tissue from the respective patients.