Hyperinsulinemia, hypertension, hypertriglyceridemia and obesity are all risk factors for atherosclerosis. The clustering of these risk factors in the same individual greatly increases the risk for atherosclerosis and has been termed 'Syndrome X' or 'The Deadly Quartet' The purpose of the present study was to investigate the effects of diet on these risk factors in inbred, female Fischer 344 rats. Animals were raised on ad lib diets consisting of high-fat, sucrose (HFS) or low-fat, complex-carbohydrate (LFCC). After 2 years, the HFS rats were obese (38% +/- 1% vs. 15% +/- 1% body fat), hypertensive (140 +/- 3 vs. 123 +/- 3 mmHg), hyperinsulinemic (439 +/- 118 vs. 98 +/- 10 pmol/l), and hypertriglyceridemic (1.1 +/- 0.2 vs. 0.4 +/- 0.07 mmol/l). The HFS rats also exhibited enhanced clotting and impaired fibrinolytic response to streptokinase. All these differences between the two groups were statistically significant (P < 0.05). Insulin was significantly correlated with body weight (r = 0.71), triglycerides (r = 0.48), and systolic blood pressure (r = 0.70). Total cholesterol was slightly, but not significantly higher, in the HFS group (2.8 +/- 0.3 vs 2.2 +/- 0.1 mmol/l) while HDL-cholesterol was unchanged. These results show that many risk factors for atherosclerosis can be induced in inbred rats by feeding a HFS diet. Aggregation of risk factors was found in the HFS group but not in the LFCC group. In fact, most of the rats on the LFCC diet developed no risk factors after 2 years, indicating that the development of risk factors is not an aging phenomenon.