The optimal duration of antiplatelet therapy was evaluated by sequential measurement of platelet accumulation on polytetrafluoroethylene (PTFE) grafts. Sixty four New Zealand white rabbits received aspirin (ASA, 10 mg/kg/day) and dipyridamole (DPM, 10 mg/kg/day) (n = 34), or placebo (n = 30), beginning 3 days prior to insertion of a 10 mm x 3 mm PTFE interposition aortic graft. Using autologous In-111 labelled platelets, a graft platelet accumulation index (GPAI) was calculated as the grafttreference aorta ratio of activity of In-111. ASA/DPM significantly reduced mean GPAI from grafts and reference aorta removed 48 h after graft insertion from 217±74 (mean±SEM) on placebo (n = 8) to 43±3 (n = 9), (p<0.05). Mean GPAI at 4 weeks were 55±28 (n = 5) and 28±6 (n = 5), (not significant), at 8 weeks 64±17 (n = 5) and 49±9 (n = 5) (not significant) and at 12 weeks 11±4 (n = 4) and 25±10 (n = 5), (not significant) for the control and ASA/DPM groups, respectively.We conclude that ASA/DPM significantly reduce early platelet deposition on PTFE grafts. These data support the use of antiplatelet therapy after vascular bypass procedures in man and further suggest that only a few months of antiplatelet therapy may be beneficial in man.