We investigated the effects of androgen modulation on the cytotoxicity of adriamycin (AD) and melphalan (MEL) on cultured cells from the androgen-responsive Shionogi mouse mammary tumor. Culture medium contained 10 ng/ml, 1 ng/ml or no dihydrotestosterone (DHT). Growth rates of cells increased with increasing concentrations of androgen. Cells cultured in 10 ng/ml DHT rapidly reached confluence and proliferation slowed. The prolonged growth phase of cells incubated in 1 ng/ml DHT rendered the cells most sensitive to the drugs for the longest period of time. Cells cultured in the absence of DHT were least sensitive to the drugs. The results suggest that combination endocrine ablation and administration of chemotherapeutic agents may not be beneficial to the clinical management of breast cancer. In contrast, hormonal manipulations that maintain the slow growth of tumors may enhance cytotoxicity of antineoplastic agents.