In a 12-week controlled clinical study of the effects of two nonsteroidal anti-inflammatory drug regimens on serum lipoproteins in patients with osteoarthritis, 54 patients were treated with naproxen, 500 mg twice daily, and 45 patients were treated with nabumetone, 1,000 mg once daily. In patients who received naproxen, the mean levels of total serum cholesterol decreased by 18.3 mg/dL (7.0%) from baseline to 12 weeks, high-density lipoprotein (HDL) cholesterol remained unchanged, and low-density lipoprotein (LDL) cholesterol decreased by 15.4 mg/dL (8.7%). In patients who received nabumetone, mean levels of total serum cholesterol increased 10.4 mg/dL (4.0%), HDL cholesterol remained unchanged, and LDL cholesterol increased 7.2 mg/dL (4.1%). Furthermore, serum triglyceride levels tended to increase in nabumetone-treated patients and decrease in naproxen-treated patients, with a statistically significant (P < 0.05) difference between treatments. The decreases in total cholesterol and LDL cholesterol levels in patients receiving naproxen were statistically significant (P < 0.01). These results confirm previous findings on naproxen's cholesterol-lowering effect.