The purpose of this study was to determine whether administration of estrogen or/and haloperidol (HAL), a drug that increases prolactin (PRL) secretion, could counteract the inhibitory effects of underfeeding on growth of established carcinogen-induced mammary cancers in rats. Sprague-Dawley female rats were fed half of the complete diet consumed daily by ad libitum fed controls, beginning 1 week before daily injection of estradiol benzoate (EB) or/and HAL for 3 weeks. Body weight, mammary tumor number, and mammary tumor diameter were measured at weekly intervals, and at the end of the 3 weeks blood was collected for assay of serum PRL. Full-fed (FF) control rats showed an increase by the end of 3 weeks in average body weight, mammary tumor number, and mammary tumor size whereas half-fed (HF) rats showed a significant decrease in average body weight, tumor number, and tumor size, and serum PRL concentrations when compared with these parameters in FF rats. Administration of EB to the HF rats partially prevented loss of mammary tumor size and significantly increased serum PRL levels over those of HF or FF control rats. Injection of HAL or the combination of HAL and EB completely prevented the decrease in mammary tumor number and size in the HF rats. These results suggest that regression in number and size of established mammary tumors in HF rats during a 3-week period is due primarily to a decrease in secretion of estrogen and PRL, the two hormones essential for mammary tumor growth in rats.