The effect of tamoxifen, a nonsteroidal antiestrogenic drug, on the in vitro growth of three cell lines derived from carcinoma of the uterine cervix (HeLa, CaSki, ME-180) was studied using the breast cancer cell line MCF-7 as a tamoxifen-sensitive control. Logarithmically growing cells were fed daily with medium containing 5% dextran-charcoal-treated fetal bovine serum (D5) and 0, 1, 2.5, 5, 7.5, or 10 microM tamoxifen. The cell number in replicate cultures was assessed every other day by cell counts. Growth inhibition was expressed as the percentage of the cell number in control cultures fed with D5. At a concentration of 5 microM tamoxifen, a clear decrease in cell proliferation, resulting in 66-74% inhibition of growth, was observed with MCF-7, HeLa, and ME-180 after 6 days of exposure to tamoxifen. Doses greater than 5 microM resulted in cytotoxicity and progressive cell loss. With the CaSki cell line, 2.5 microM tamoxifen induced more than 60% growth inhibition and 5 microM tamoxifen was cytotoxic. Tamoxifen-induced growth inhibition was reversed by removing tamoxifen from the cell cultures, and the cells resumed logarithmic growth after a lag period of 24-48 hr. MCF-7, but not the cervical carcinoma, lines required estradiol for complete and rapid recovery of logarithmic growth. Our results indicate that tamoxifen inhibits cell growth of these cervical carcinoma cell lines by a mechanism different from that in MCF-7.