Experiments were performed to determine PRL and GH concentrations in mice rendered obese by chemical means and to compare these concentrations with those of mice obese as a result of genetic mutation. Basal levels of serum PRL and GH were generally lower in gold thioglucose (GTG) and bipiperidyl mustard (BPM)-treated obese mice compared with lean controls. In the pituitary gland, the hormonal changes varied from lower or unchanged levels of PRL and GH shortly after drug injection to very high concentrations of PRL (but not of GH) a year later. However, when the mice were challenged with perphenazine, a drug that causes prompt release of PRL, GTG and BPM-obese mice released 2-5 times as much PRL as did lean controls, suggesting an impairment in the hypothalamic control of PRL secretion in GTG/BPM-obese mice. Basal levels of PRL and GH in genetically obese (ob/ob) mice of both sexes were also lower than those in their lean relatives (?/+). This was true for both serum and pituitary concentrations of the two hormones, the only exception being pituitary GH concentrations in females which were higher than or equal to those of controls. However, unlike GTG and BPM-obese mice, genetically obese mice released very little PRL compared with their lean relatives when stimulated with perphenazine, which suggested an insufficiency of pituitary function in ob/ob mice. The results demonstrate abnormalities in the secretion of PRL and GH in obese mice of both types.