Polygenic obese (M16) and nonobese (ICR) mice were fed ad libitum either a high-fat (FAT) or high-carbohydrate (CHO) diet from 6 to 10 weeks of age. After this four-week period, M16 exceeded (P less than 0.01) ICR mice and FAT-fed exceeded (P less than 0.01) CHO-fed mice in body energy percent, body fat percent, and weight and proportional weight of epididymal and subcutaneous fat pads. Fat cell size and number in both fat depots were greater (P less than 0.01) in the M16 than in the ICR line. Mice fed FAT had larger (P less than 0.01) fat cells in both depots compared with CHO-fed mice, but fat cell nuber was not altered significantly. M16 mice were hyperglycemic, hyperinsulinemic and hypercholesterolemic, Dietary treatment did not affect glucose or insulin levels, but cholesterol was greater (P less than 0.01) on FAT than on CHO diet. Lipoprotein lipase and fatty acid synthetase activities were greater in M16 than in ICR mice, while fatty acid synthetase activity was greater in mice fed CHO than in those fed FAT. Genotype by diet interactions were not important for the traits studied. Polygenic obese mice, developed by selection for increased growth rate, share many of the characteristics of the single gene obesity syndromes in rodents. The development of obesity in polygenic obese mice may be due, in part, to an acceleration of the normal developmental process of growth, in addition to hyperphagia and increased energetic efficiency.