We investigated plasma lipoprotein profiles and the activities of tissue cholesterol regulating enzymes in Wistar fatty rats, an animal model for non-insulin-dependent diabetes mellitus (NIDDM). Wistar fatty rats were made by transfer of the fa gene to the Wistar Kyoto rats by backcross-breeding. Wistar fatty and control non-diabetic littermates were given a laboratory chow or an atherogenic diet containing 1 percent (weight percent) cholesterol, 0.5 percent cholic acid, and 5 percent lard. Under the chow diet, plasma fasting glucose and immunoreactive insulin concentrations in Wistar fatty rats were 1.5- and 6-fold higher than controls, respectively. Plasma cholesterol was significantly increased in Wistar fatty rats compared with controls. Elevated plasma cholesterol levels in Wistar fatties was accounted for by the increases of cholesterol content in the d less than 1.006 g/ml lipoprotein and high-density lipoproteins. Under the atherogenic diet, plasma cholesterol levels in Wistar fatties were further increased by 129 percent compared with controls. The diet-induced increase of cholesterol contents was shown in all lipoprotein classes for Wistar fatty rats. The activities of regulatory enzymes for cholesterol biosynthesis or absorption were measured in Wistar fatty rats. Both hepatic and intestinal 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activities were significantly higher in Wistar fatty rats than those in controls (P less than 0.05 and P less than 0.01, respectively). ACAT activities in Wistar fatties were significantly increased in the intestine (P less than 0.05) and decreased in the liver in comparison with controls (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)