Female Sprague-Dawley rats with established 7, 12-dimethylbenz(a)anthracene-induced mammary tumors were given daily s.c. injections of 50 microgram dexamethasone per rat, 0.5 mg haloperidol per kg, or both for 3 weeks. Control rats received the injection vehicles only. Mammary tumor growth was measured at weekly intervals for 21 days, and blood was collected on Days 10 and 21 of treatment for assay of prolactin. Dexamethasone produced significant regression of mammary tumors and reduced serum prolactin levels, whereas haloperidol significantly increased mammary tumor growth and greatly elevated serum prolactin levels. When dexamethasone and haloperidol were injected together, there was significant regression of mammary tumors despite markedly elevated serum prolactin levels. No significant differences in specific prolactin binding to membrane preparations of mammary tumors from these animals were observed in any treatment group. These results indicate that dexamethasone, a synthetic glucocorticoid, can directly inhibit mammary tumor growth in the presence of elevated serum prolactin levels produced by haloperidol, and this inhibition is not due to a reduction of prolactin binding sites in the tumor tissue.