Twice-daily injections of 3 doses of synthetic thyrotropin-releasing hormone (TRH), a hormone normally produced by the hypothalamus, produced significant increases in size and number of 7,12-dimethylbenz(a)anthracene-induced mammary cancers over 0.87% NaCl solution injected control rats. When thyroidectomized rats, bearing 7,12-dimethylbenz(a)anthracene-induced mammary tumors were given the same twice daily injections of TRH, mammary tumor growth was increased to the same extent as in intact rats given TRH, showing that the effects of TRH were not exerted via stimulation of thyroid function. The TRH-induced increments in mammary tumor growth were accompanied by increases in serum prolactin levels over 0.87% NaCl solution injected controls. A single daily injection of 2-bromo-.alpha.-ergocryptine (CB-154), a prolactin release inhibitor, blocked TRH-induced mammary tumor growth and reduced serum prolactin values. This indicates that a twice daily pulse of TRH can stimulate mammary tumor growth by releasing prolactin from the anterior pituitary.