The particle-size effect of benoxaprofen, a new nonsteroidal anti-inflammatory agent, on the in vitro dissolution rate and oral absorption in humans was evaluated. Ten normal subjects participated in a randomized crossover-designed absorption study with two sieved particle-size formulations: one with crystals larger than 60 mesh (mean equivalent spherical diameter = 640 micron) and the other with crystals smaller than 100 mesh (mean equivalent spherical diameter = 67 micron). Plasma drug concentrations and urinary drug excretion were used to determine the relative absorption of the two formulations. The standard USP procedure was used for the dissolution study. Particle size had a dramatic effect on both the in vitro drug dissolution and its oral absorption in humans. In vitro, the smaller crystals dissolved more rapidly and more efficiently than the larger crystals. In vivo, the smaller crystals produced higher plasma concentrations, more rapid peak concentration attainment, and more drug excreted in the urine.