The effect of selenium was examined on the growth potential of normal, preneoplastic and neoplastic mammary cells grown in primary monolayer cell cultures and on 3 established mammary cell lines. Selenium, present as Na2SeO3 in serum-free DMEM, inhibited all mammary cell cultures at 1 x 10(-5) M. Selenium, at 5 x 10(-8) M, stimulated the growth of primary cell cultures of normal mammary cells and C4 preneoplastic cells and the established cell line YN-4, but not the growth of D2 preneoplastic cells and tumors in primary cell cultures and of established cell lines CL-S1 and WAZ-2t. The differential responses of cells from preneoplastic outgrowth lines C4 and D2 and of D2 primary tumors in vitro correlated with the sensitivity of these same cell populations to selenium-mediated inhibition of growth and tumorigenesis in vivo. The differential responses among the 3 cell lines will allow further comparative studies on the cell biological basis of selenium function.