The immunoregulatory effect of Catrix on in vitro and and in vivo antibody production was examined in mice. Catrix, an acidic mucopolysaccharide complex, contains glycosaminoglycans including chondroitin sulfate. Catrix-S, a soluble derivative, was found to enhance T-dependent and T-independent antibody responses in vivo in a dose-dependent manner, with 100 mg intraperitoneally or 10 mg intravenously being optimal. Lower doses were found to be less effective or inhibitory. In vitro, the enhancing activity of Catrix-S on proliferative response was additive with that of dextran sulfate and lipopolysaccharide but not with chondroitin sulfate C. This immunoaugmenting activity appears to be related to the chondroitin sulfate component of Catrix-S, because both have similar effects on in vivo and in vitro antibody responses and because chondroitinase ABC inactivates activity. The inhibitory activity of Catrix-S could be separated from its stimulatory effects by ammonium sulfate precipitation or by fractionation according to molecular weight. The immunoaugmenting effect was present in the 0-30% saturated ammonium sulfate precipitate and in the 5-10,000-m.w. and 30-100,000-m.w. fractions. The ability of Catrix-S to enhance antibody responses in nude as well as in normal mice, and antibody responses to T-independent as well as to T-dependent antigens, indicates that its activity is due in part to a direct effect on B cells and/or to an indirect effect mediated by macrophages.