Certain scrapie strains cause obesity in several strains of mice. The potential association between obesity and altered glucose tolerance was assessed by monitoring body weight and glucose tolerance throughout the incubation period in scrapie strain-mouse strain combinations that do and do not produce obesity. Virtually all obese mice showed reduced glucose tolerance as shown by significantly higher blood glucose levels 2 h after a glucose overload. Mice injected with a scrapie strain that did not cause obesity showed normal tolerance. The scrapie infectivity titre of the pancreas of obese mice clinically affected with scrapie was very low. Adrenalectomy prevented both the increase in weight and aberrant glucose tolerance but had no other effect on the course of the disease. Following increasing dilution of the inoculum, the increase in body weight and the development of aberrant glucose tolerance reached an end-point that was similar to that of scrapie infectivity. The system described provides an inducible model of obesity with altered glucose tolerance.