Radioactive labeled protein and platelet studies suggest that an ideal vascular surface absorbs albumin and prevents platelet adherence and aggregation. This study examines the interaction of serum and plasma proteins, white cells, and platelets in the thrombotic response to small internal diameter vascular prostheses. Thirty-seven replamineform silicone rubber vascular prostheses, 4 mm internal diameter and 6 cm length, had 5% aspirin and 5% theophylline by weight dispersed in a luminal coating (D); the remaining 37 control (C) prostheses had an identical silicone rubber coating without drugs. Scanning electron and darkfield microscopy confirmed similar surface topography in C and D grafts. One C and one D graft were studied in parallel using a modified canine arteriovenous fistula. Consistently, D prosthesis had increased bleeding through the graft wall. The 7 serum and 8 plasma experiments demonstrated greater accumulation on the D prostheses, the greatest deposition occurring within the first 30 minutes. In 8 platelet experiments, D grafts accumulated more radioactivity at both the 5 and 30 minute intervals. Six mononuclear and 8 PMN experiments had less accumulation on the D grafts at 15 minutes and no consistent difference at 60 minutes. Elution of C and D Grafts demonstrated significant drug levels in only the D grafts at the beginning of the experiments and after 15 minutes of exposure of blood. We conclude: (1) aspirin and theophylline have an effect on the initial interaction of plasma proteins, platelets and white cells in the thrombogenic response, (2) the effect diminishes as time released drug levels decrease.