To compare the lipid-regulating effects and steady-state pharmacokinetics of rosuvastatin, a new synthetic hydroxy methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, following repeated morning and evening administration in volunteers with fasting serum low-density lipoprotein cholesterol (LDL-C) concentrations < 4.14 mmol l-1. In this open-label two-way crossover trial 24 healthy adult volunteers were randomized to receive rosuvastatin 10 mg orally each morning (07.00 h) or evening (18.00 h) for 14 days. After a 4 week washout period, volunteers received the alternative regimen for 14 days. Rosuvastatin was administered in the absence of food. Reductions from baseline in serum concentrations of LDL-C (-41.3%[morning]vs-44.2%[evening]), total cholesterol (-30.9%vs-31.8%), triglycerides (-17.1%vs-22.7%), and apolipoprotein B (-32.4%vs-35.3%) were similar following morning and evening administration. AUC(0,24 h) for plasma mevalonic acid (MVA), an in vivo marker of HMG-CoA reductase activity, decreased by -29.9% (morning) vs-32.6% (evening). Urinary excretion of MVA declined by -33.6% (morning) vs-29.2% (evening). The steady-state pharmacokinetics of rosuvastatin were very similar following the morning and evening dosing regimens. The Cmax values were 4.58 vs 4.54 ng ml-1, and AUC(0,24 h) values were 40.1 vs 42.7 ng ml-1 h, following morning and evening administration, respectively. There were no serious adverse events during the trial, and rosuvastatin was well tolerated after morning and evening administration. The pharmacodynamic effects and pharmacokinetics of rosuvastatin are not dependent on time of dosing. Morning or evening administration is equally effective in lowering LDL-C.