Statins are regarded as efficacious in general but there is a wide variation in individual response. We sought demographic and lifestyle factors that influenced the response to pravastatin 40 mg/day in moderately hypercholesterolemic men in the West Of Scotland Coronary Prevention Study (WOSCOPS). Changes in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol after 6 months of treatment were examined in 1,604 highly compliant subjects. LDL cholesterol decreased by a mean of 30.4%. The magnitude of the change was influenced, albeit to a small extent, by baseline plasma triglyceride levels and alcohol intake and age; subjects with low plasma triglyceride levels, older subjects, and subjects with low alcohol intake had the greatest reductions. The mean response in HDL cholesterol in the group was an 8.3% increase (0.09 mmol/L). The percent increase in HDL cholesterol was affected by baseline HDL level, plasma triglyceride levels, decrease in plasma triglyceride levels during the administration of pravastatin, and body mass index. The absolute increase in HDL cholesterol was influenced by the decrease in plasma triglyceride levels, body mass index, and alcohol intake. All of these associations were weak (r <0.2) although highly significant. In conclusion, plasma lipid phenotype, obesity, and alcohol consumption appear to influence the response of LDL and HDL cholesterol to statin treatment. The absolute increment in HDL cholesterol is relatively constant across a range of baseline values, hence the percent change is largely a function of the starting value.