Extensive surveys for the effects of various β- d-glucans on the coagulation cascade in horseshoe crab amebocyte lysates showed that low-mol-wt-(1 → 3)-β- d-glucans and laminaran oligosaccharides inhibit the activation of a limulus coagulation factor G by high-mol-wt-(1 → 3)-β- d-glucans. The inhibitory properties are exclusively dependent upon their number-average mol wt ( M n) in a range of 342-58 100, which correspond to a degree of polymerization (dp) range of 2–359. The most effective is a laminaran dextrin of M n 5800 (dp of 35–36), which causes 50% inhibition of factor G activation at a concentration of 3.16 ng/mL. The inhibition of the activation of factor G proportional to the concentration of the inhibitor, and the adsorption of factor G by inhibitory β- d-glucan-conjugated cellulose suggested a high affinity of the inhibitory saccharides for the activator-recognition site of factor G. Branched (1 → 6), (1 → 3)-β- d-glucans, laminarans, mixed linkage (1 → 3), (1 → 4)-β- d-glucans, and partially substituted curdlan and laminaran were found to be inhibitory, possibly owing to clusters of consecutive (1 → 3)-β- d-glucopyranosyl residues as intrachain units. The inhibition appears to be related to the inability of the inhibitory (1 → 3)-β- d-glucans to form ordered conformations and to their tendency to take a random-coil structure in aqueous solution.