This study assessed steady-state azimilide pharmacokinetics and pharmacodynamics in 119 healthy male and female volunteers. Parallel groups of 18-40-year-old subjects received doses of 35, 100, 150 or 200 mg day(-1) for up to 14 days, with 1, 2 or 3 days of loading. Another group of > 55-year-old subjects received 100 mg day(-1) with a 3-day loading regimen. There was a slight overshoot of steady-state (24%) after loading, but concentrations decreased to steady-state by day 7. Mean peak steady-state azimilide concentrations ranged from 186 to 1030 ng mL(-1) across the 35-200 mg day(-1) dose range, while mean trough steady-state azimilide concentrations ranged from 108 to 549 ng mL(-1). Azimilide pharmacokinetics were proportional to dose, except for renal clearance, and did not differ between 18-40-year-old and > 55-year-old subjects. Pharmacodynamics did not differ across dose groups. The mean maximum effect (Emax) ranged from 24 to 28% change in QTc from baseline. The concentration needed to attain one half Emax ranged from 432 to 542 ng mL(-1) across dose groups. Equilibration was rapid between blood and the biophase, with equilibration half-lives of less than 1 min.