Beraprost sodium (BPS) is an orally stable analogue of prostacyclin that inhibits adenylate-cyclase dependent platelet aggregation and is proposed for treatment of chronic arterial occlusion. To determine the duration and intensity of platelet antiaggregation with BPS, 12 healthy, nonsmoking, male white volunteers participated in a double-blind, dose-escalating design with randomized placebo, placebo-controlled, cross-over study. After overnight fasting, single (20,40, 60 μ.g and placebo) and repeated [20, 40, 60 μg and placebo three times daily (t.i.d.) for 3 days] oral doses of BPS were administered. Mean percentage of inhibition of ADP-induced aggregation normalized to placebo was measured for 8 h after drug administration and related to plasma concentrations (Cp) of the active enantiomer (APS 314d). BPS 40 and 60 (Ag decreased platelet aggregation 1 h after single doses, and 0.5 h and 1 h after repeated doses. BPS 20 μg had no significant effect. APS 314d pharmacokinetics was linear, and its terminal half-life (t) ranged from 0.50 ± 0.21 to 0.91 ± 0.27 h (mean ± SD) independently of BPS dose. Antiaggregating effects were poorly related to Cp of APS 314d (r2 ≤ 0.2). Some subjects complained of moderate postdrug absorption headaches (7 of 12 after single and 8 of 12 after repeated doses) and flushes (6 of 12 and 7 of 12, respectively). These data indicate that orally active prostacyclin BPS (40 or 60 μg) exerts its maximal antiaggregating effects between 0.5 and 1 h.