Eleven weeks of exposure to diethylstilbestrol (DES) releasing capsules caused marked changes in neuroendocrine function in male rats sacrificed 22 months later. Plasma prolactin levels were increased and plasma LH levels were decreased in the DES-exposed as compared to the control animals. DES-treated animals had significantly decreased levels of dopamine (DA) in the median eminence and lower rates of DOPA accumulation after blockade of aromatic amino acid decarboxylase than did the control animals. Norepinephrine and serotonin content and 5-hydroxytryptophan content in the ME, the medial basal and the anterior hypothalamus were not significantly affected by DES treatment. Basal prolactin release in vitro was reduced in the DES animals while prolactin responsiveness to inhibitory effects of 10<sup>–7</sup> M DA was enhanced. From these data it appears that a relatively brief exposure to DES in early adulthood causes marked and persistent changes in tuberoinfundibular DA function that are responsible for continued hyperprolactinemia. Associated reductions in LH secretion also appear to be due to hypothalamic as opposed to pituitary factors.