The objective of this study was to develop and validate a simple clinical index to identify individuals at increased risk of an elevated CHL/HDL ratio. Using recursive partitioning, factors associated with an elevated CHL/HDL ratio were identified among 1993 men and 1631 women in the Lipid Research Clinic Prevalence Study. These factors were weighted using logistic regression analyses to develop a clinical index that was validated on 486 men and 484 women reported in the Santé Québec cardiovascular health survey. A high CHL/HDL ratio was defined as > or =5 for women and > or =6 for men which approximates the 75th percentiles reported in the second United States National Health and Nutrition Survey. In the Lipid Research Clinics cohort, 307 men (15.4%) and 188 women (11.5%) had an elevated CHL/HDL ratio. Using separate clinical indices for men and women, significant variables included body mass index, alcohol consumption, age, smoking status, systolic blood pressure, physical activity status, and the presence of diabetes, the study identified 88% of the men and 82% of the women with elevated ratios. External validation using the Santé Québec data set demonstrated test sensitivities of 81% for men and 94% for women. Overall, 12% of those with a high CHL/HDL ratio were misclassified as low risk. The ratio of total plasma cholesterol to HDL cholesterol has been shown to be one of the best lipid predictors of increased coronary risk. Readily available clinical data can be used to identify 88% of those individuals most likely to benefit from lipid screening while obviating the need for such screening in one quarter of otherwise healthy adults.