MK-886, a leukotriene biosynthesis inhibitor, was evaluated in double-blind, placebo-controlled, randomized single- and multiple-dose studies in 12 and 24 healthy male subjects, respectively. The effects of a single dose (250, 500, and 750 mg) and multiple doses (100 mg and 250 mg every 8 hours) of MK-886 on calcium ionophore stimulated leukotriene B4 synthesis ex vivo in whole blood were evaluated. Inhibition of leukotriene B4 biosynthesis ex vivo occurred in a dose-related manner up to a 500 mg single dose, and 250 mg every 8 hours. A single dose of 500 mg MK-886 significantly inhibited leukotriene B4 biosynthesis by a maximum of 60% at 2 hours after the dose (p < 0.05). Multiple doses of 250 mg significantly inhibited leukotriene B4 biosynthesis by a maximum of 52% at 2 hours after the dose (p < 0.05). The degree of leukotriene B4 inhibition ex vivo in whole blood significantly correlated with plasma MK-886 concentrations (r = 0.78). In conclusion, the single and multiple doses of MK-886 evaluated in this study were well tolerated overall and partially inhibited leukotriene B4 biosynthesis ex vivo in whole blood.