Dextran has been shown to alter the mechanical properties and lysability of fibrin. The present study was undertaken to determine whether it would also influence the ability of polymerizing fibrin to activate platelets. Human fibrinogen, with or without the presence of dextran, was incubated with either human thrombin or reptilase at 37 C. Macroscopically evident fibrils first appeared at 7 1/2 to 8 minutes in fibrinogen solution not containing dextran and at 2 1/2 to 3 minutes in solution containing dextran. Both solutions caused aggregation of washed human platelets, but the one containing dextran was less potent (P less than 0.005). Similarly, polymerizing fibrin, under the influence of dextran, was a less potent stimulator of platelet release of labeled serotonin. Scanning electron microscopy showed decreased platelet adhesion to fibrin polymerized in the presence of dextran. Inclusion of dextran in plasminogen-rich bovine fibrin clots facilitated their lysis by urokinase. Apparently, dextran not only increases the lysability of fibrin but also alters the platelet-activating activity of polymerizing fibrin.