Three groups of male mice were fed three different diets for about 3 weeks: powdered chow (C), a high fat (F) diet (chow:Crisco, 2:1), and a high dextrose (D) diet (chow:dextrose, 2:1). Food and water intake and body weights (BWts) were measured daily. On Day 20 of the study, mice were injected IP with 0.3 mg/g of goldthioglucose (GTG). Two days later, the mice were sacrificed and brains were removed for histological examination of GTG-induced lesions in the ventromedial hypothalamus (VMH). It was found that (1) F-fed mice ate more and gained more BWt than C- and D-fed mice, and (2) the average GTG lesion volume of F-fed mice was twice as large as those of C- and D-fed mice. In view of known alterations in sensitivity of the VMH to goldthioglucose with changes in glucose metabolism, it is suggested that the larger goldthioglucose induced lesions in F-fed mice may be due to elevated blood levels of goldthioglucose or altered glucose metabolism in goldthioglucose sensitivity cells in the VMH.