Study Objective. To assess the efficacy and safety of HMG-CoA reductase inhibitors (statins) in patients with human immunodeficiency virus (HIV) infection and hyperlipidemia. Design. Retrospective analysis. Setting. HIV clinic. Patients. Twenty-six HIV-infected patients with hyperlipidemia. Intervention. Five patients received pravastatin, 13 lovastatin, 10 simvastatin, and 2 atorvastatin (total 30 courses). Measurements and Main Results. Reductions in cholesterol and triglycerides were used to assess efficacy; creatine kinase (CK), liver enzymes, and myalgia were markers of statin toxicity. After a median of 8.2 and 7.2 months of treatment, the agents collectively reduced median baseline total cholesterol 27% (354 to 263 mg/dl) and triglycerides 15% (513 to 438 mg/dl), respectively. Two patients, one with marked CK elevations, experienced myalgias with lovastatin, and two experienced transaminase elevations 3 or more times the upper limit of normal. Conclusion. Statins are effective in reducing total cholesterol and triglycerides in HIV-infected patients, although lipid levels infrequently return to normal. Lovastatin should be avoided in patients receiving concomitant drugs that may potentiate skeletal muscle toxicity with this agent.