The St. Thomas' Atherosclerosis Regression Study (STARS) showed that treatment of mild hypercholesterolemia with diet or diet plus cholestyramine favorably influences the course of coronary heart disease (CHD) over 3 years in middle-aged men. The study employed quantitative angiography to measure change in coronary luminal dimensions. Angiographic benefit was paralleled by improvement in clinical outcomes. The study allowed a detailed analysis of the nutritional, metabolic, and genetic determinants of the progression of CHD. Significant associations were found between changes in both focal and diffuse estimates of coronary atherosclerosis and the plasma concentrations of low-density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B, dietary intake at total and saturated fat, and polymorphisms of the apo-AI gene promoter region and angiotensin-converting enzyme (ACE) gene. Up to 38% of the variance in the progression of CHD could be explained by the independent effects of LDL cholesterol and dietary intake of saturated fat. The ACE genotype was only an independent predictor of the progression of CHD in patients whose LDL cholesterol had been substantially reduced with diet and cholestyramine. The clinical significance of the nutritional, metabolic and genetic findings is discussed.