The polyanion dextran sulphate (DS) triggers the alternative pathway of complement. The influence of the molecular weight and degree of sulphation on this potency was studied. The degree of substitution turned out to be the critical parameter for optimal C3 turnover: 60 SO4/100 glucose units (Glc) showed optimal activity; an increase up to 190 SO4/100 Glc did not increase the activation potency, while lowering the degree of sulphation diminished this activity. DS preparations (120 SO4/100 Glc) of molecular weight: 1 x 10(4); 8 x 10(4); 2-5 x 10(5); 2 x 10(6) were equally active; a DS of molecular weight 5 x 10(3) was inactive. These results indicate that above a critical molecular size (greater than 5 x 10(3)) only the degree of substitution is responsible for the C3 activating capacity. Clusters of several glucose residues each carrying one or two sulphate groups are thought to be the essential structure in DS for the activation of the alternative pathway.