Effects of (1----3)-beta-D-glucans on clot formation of human plasma were examined. Gel forming 6 branched (1----3)-beta-D-glucans, SSG, branched at every other main chain glucosyl unit, grifolan (GRN) and schizophyllan, branched at one third of main chain glucosyl unit, enhanced clot formation of human plasma. GRN derivatives also increased the contents of clot, but less effectively than GRN. This effect was dependent on dose, molecular weight (greater than 20K), side chain (branching), and ultrastructure (single chain conformer) of the beta-glucans. It may be important for the mechanism of (1----3)-beta-D-glucan induced enhancement of plasma clotting to activate factor XII, to bind with fibrinogen, and to increase the local concentration of the clotting system by steric exclusion.