In dogs with prosthetic aortic grafts, we have documented chronic changes in circulating platelets (Circulation 58: II-225, 1978). Following placement of grafts, serotonin (5HT) levels decreased from 2.01±0.22 to 1.37±0.17 mg/10 platelets (p < .005). Serotonin levels remained low for up to 6 months after graft placement and returned to normal when platelet survival time (PST) began to normalize. Maximum in vitro uptake of 14C-5HT was depressed after graft placement (89.0±0.71 before vs 72.0±1.11% after, p <.001), but time to achieve maximum uptake was much less (16.5±2.4 before vs 5.0±2.8 sec. after, p <.001). In vivo release of 5HT was assessed by labelling autologous platelets with 51Cr and 14C-5HT. In animals with grafts, PST was shortened but 14C label survived 1.55±0.10 times longer than 14Cr label. This was significantly greater (p <.02) than control animals with, normal PST in whom 14C label survived 1.21±0.05 times longer than 51Cr. The ratio of 14C/51Cr activity over 5 days following infusion of double labelled platelets increased from 3.16±0.52 (day 1) to 5.85±1.18 (day 5), p <. 001. Among controls, this ratio increased only slightly (1.99±0.34 to 2.26±0.42) and was significantly less on days 2 thru 5 than in animals with grafts (p <. 05–.005). Urinary 5HIAA excretion, measured for 2 months before and after graft placement, increased from 2644.9±80.6 to 3091.2±96.4 μg/gm creat./day (p <.001). In these animals, we conclude that platelets interact with the prosthetic surface, release 5HT and recirculate. Reutilization of released 5HT occurs but may be limited by depressed uptake. The net effect is a reduction in platelet 5HT.