The 2 most important hormones for development and growth of mammary tumors in rats are prolactin and estrogen, both under control of the pituitary gland and the brain. Estrogen stimulates prolactin secretion and acts with prolactin directly on the mammary tissues to promote tumorigenesis. Large doses of estrogen can inhibit mammary tumor growth, not by suppressing prolactin secretion but by interfering with the peripheral action of prolactin on the mammary tissues. Estrogen can neither induce nor maintain growth of mammary tumors in the absence of the pituitary, but prolactin may have a limited capacity to induce and maintain mammary tumor growth in the absence of the ovaries. Although rats show no significant change in serum-prolactin levels during growth of carcinogen-induced mammary tumors, elevations of serum prolactin produced by hypothalamic lesions, pituitary grafts, or administration of small doses of estrogen or appropriate drugs, can increase growth of spontaneous and carcinogen-induced mammary tumors. Drugs that reduce serum-prolactin levels, including ergot derivatives, iproniazid, pargyline, etc., can decrease growth of mammary tumors. When prolactin secretion is elevated before administration of a carcinogen, development of mammary tumors is inhibited, presumably by stimulating growth of mammary tissues and thereby rendering them refractory to the action of the carcinogen. Biogenic amines in the hypothalamus apparently serve as neurotransmitters to regulate the release of prolactin-inhibiting factor, luteinizing-hormone releasing Factor, and follicle-stimulating hormone releasing Factor, which in turn regulate release of prolactin, luteinizing hormone, and follicle-stimulating hormone by the pituitary. Any agent that can alter biogenic amine turnover in the hypothalamus is therefore potentially useful for controlling growth of mammary tumors.