The effect of food on the bioavailability of GW420867X, a novel nonnucleoside reverse transcriptase inhibitor, was investigated in 15 young, healthy, male volunteers. A single oral dose of GW420867X 100 mg was administered in the fasted state, after a high-fat meal, and after a meal of normal fat composition. Tolerability and pharmacokinetic sampling were assessed at baseline and up to 600 hours. The median concentration-time plots for each treatment group were essentially superimposable. Neither the rate nor the extent of absorption of GW420867X was significantly affected by food. The median time to peak plasma concentration was 3 to 4 hours, irrespective of treatment. Pairwise comparisons using the fasted treatment as the comparator showed no impact of food on GW420867X pharmacokinetics. GW420867X was well tolerated. There were no serious or treatment-limiting adverse events; all episodes reported were rated as mild to moderate. The bioavailability of GW420867X was unaffected by food. GW420867X may be administered independently of food and fat intake.