To investigate the long-term effects of efavirenz on cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL-C) and triglycerides (TG). Thirty-four HIV-infected patients who commenced efavirenz therapy were monitored for 36 months. In patients with baseline HDL-C < 40 mg . dL(-1) an increase in HDL-C from 31 +/- 1 mg . dL(-1) to 44 +/- 2 mg . dL(-1) (95% confidence interval 5.9, 21.9, P < 0.01) was observed and remained throughout the follow-up period. Median efavirenz plasma concentration was 1.98 mg . L(-1) and a direct correlation between percentage of HDL-C variation or TC/HDL-C ratio and efavirenz plasma concentrations was found. There is evidence of a long-term and concentration-dependent beneficial effect of efavirenz on HDL-C in HIV-infected patients.