Hemodialysis is associated with platelet deposition in polytetrafluoroethylene (PTFE) graft fistulas. We determined whether aspirin or ticlopidine would modify this response. Patients on chronic hemodialysis with forearm loop PTFE fistulas were studied. Platelets labeled with 111indium were injected and a baseline scan of the fistula arm was made with a large field of view gamma camera. After a routine dialysis treatment, a second scan was performed within 1 hour. Four weeks later, a repeat labeled platelet study was conducted after taking either aspirin 325 mg/d or ticlopidine 250 mg/d orally for 7 days. Images were computer analyzed by drawing seven standardized regions along each graft. The counts per second per pixel in postdialysis images were compared with predialysis images for each region and a percent uptake compared with the predialysis image was calculated. Regions with dialysis-induced uptake of more than 1.5-fold compared with the predialysis image before antiplatelet drug therapy were compared with these same regions after therapy. Six patients were studied before and after aspirin therapy. Uptakes larger than 1.5-fold over predialysis images were found in 12 of 40 regions and were 292% +/- 50% (+/-SEM) before and 193% +/- 25% of predialysis values after aspirin (P = 0.02, paired t-test). Uptakes in the remaining regions were 107% +/- 4% before and 115% +/- 6% after aspirin (P = NS). A second group was studied before and after ticlopidine (n = 5). Uptakes increased by more than 1.5-fold compared with predialysis images in 19 of 30 regions and had a median of 286% increased uptake (mean, 785% +/- 374%) before and 160% (153% +/- 10%) after drug therapy (P < 0.001, Wilcoxon). Uptakes in the remaining regions were 116% +/- 5% before and 134% +/- 13% after drug therapy (P = NS). Platelet aggregation studies suggested compliance with both drugs. These studies show that these antiplatelet drugs reduce, but do not completely prevent, dialysis-associated radiolabeled platelet deposition in PTFE grafts.