Tolerance and pharmacokinetics after single-dose administration of atorvastatin, an investigational inhibitor of HMG-CoA reductase, were examined in 22 healthy volunteers in a three-period, partially-blinded study. Participants received capsule and solution doses of atorvastatin (0.5 to 120 mg) and placebo at weekly intervals. Atorvastatin was well tolerated at doses as high as 80 mg. The adverse event profile was similar after administration of atorvastatin capsules and placebo. Atorvastatin solution was slightly less well tolerated. The most common side effect after administration of capsules and solution was headache, followed by sporadic reports of diarrhea, flatulence, and nausea. At the 120-mg solution dose, one participant experienced mild, transient restlessness, euphoria, and mental confusion that were considered to be dose-limiting side effects. Mean concentrations of atorvastatin, maximum concentration (Cmax), and area under the concentration-time curve from time 0 to the time of the last detectable concentration (AUCo-tldc) increased with increasing dose. Plasma elimination half-life (t1/2) ranged from 14.7 to 57.6 hours. The bioavailability of atorvastatin capsules was similar to that of solution. These results suggest that atorvastatin is well tolerated after single doses as high as 80 mg, and may require administration only once daily.