To determine the effect of continuing medical education (CME) on compliance with the recommendations of the National Cholesterol Education Program Expert Panel on high serum cholesterol levels in adults, we randomly assigned primary physicians in 174 practices to 3 groups, 2 that underwent either standard or intensive CME and a control group. The standard CME group was offered a free 3-hour seminar on high serum cholesterol levels; the intensive CME group was offered in addition follow-up seminars and free office materials. After 18 months, we audited 13,099 medical records from the 140 practices that remained in the study. There were no significant differences (P > .15) in screening for high serum cholesterol or compliance with guidelines between the groups receiving continuing medical education (51% screening; 33% compliance) and the control group (57% screening; 37% compliance). In the prespecified subgroup of patients with hypercholesterolemia, there was a trend toward a modest benefit from the continuing medical education interventions: compliance was 21% in the control group, 23% in the standard CME group, and 27% in the intensive CME group (P = .07 overall). These results emphasize the need for better ways to change behavior in practicing physicians and the importance of studying the implementation of preventive health recommendations.