3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors are gaining widespread use in the treatment of hypercholesterolemia. Clinical experience with lovastatin, which is approaching 4 years in many patients, indicates that it is well tolerated. Short-term adverse effects have usually been self-limited and have included abdominal pain, cramps, bloating, and flatus in 4-6% of cases. Raised hepatic transaminases and myopathy have occurred in 1.3 and 0.1% of cases, respectively; both, however, are reversible upon discontinuation of drug. To date, there is no evidence that lovastatin adversely affects the human lens. Overall, the drug has been well tolerated by the vast majority of patients over the long term. Early clinical experience with simvastatin shows a pattern and frequency of side effects similar to that reported with lovastatin.