Plasma high-density lipoprotein (HDL)-cholesterol and lipid levels were measured in 12 male marathon runners (mean age, 40 years) who ran an average of 28 km/day for ten days, rested 70 hours, then continued to run for eight more days, covering a total distance for both running periods of 500 km. Blood samples were obtained on eight mornings. After one week of running, HDL-cholesterol levels increased 18% and triglyceride levels decreased 22%. However, the three-day rest period reversed these changes. As running resumed, HDL-cholesterol levels again increased and triglyceride levels decreased. There were no significant changes in total cholesterol, body weight, or skinfold thickness despite an average caloric intake of 4,800 kcal/day. Heavy beer drinking had no discernible effect on HDL-cholesterol levels, but may have caused mild hepatic injury as suggested by significantly increased serum alanine transferase and γ-glutamyl transferase values. This study demonstrates that HDL-cholesterol levels increase with higher running mileage and decrease within days of stopping exercise when caloric and alcohol intake remain elevated.