Mice with the recessively inherited obese-hyperglycemic syndrome (ob/ob) and their nonobese litter mates were studied over a 26-week period. The body weights and serum glucose levels of ob/ob mice began to rise markedly at 5-6 weeks of age and remained elevated throughout the period of study. Obese mice were significantly heavier (P less than .001) and had higher serum glucose levels (P less than .001) than lean mice, but obese mice had variably lower serum growth hormone (GH) and prolactin (PRL) levels (P less than .001) than lean litter mate controls after 4-5 weeks of life. A 24 h rhythm study performed on 15-week-old mice revealed a relatively unaltered but attenuated pattern of GH and PRL secretion in ob/ob mice. During and after the development of the obese-hyperglycemic syndrome, the low levels of these two hormones probably indicates an altered hypothalamic regulation of pituitary function.