Four kinds of acidic heteroglycan, T3a-T3d, were isolated from the body of the fungus Tremella fuciformis Berk. The molecular weights of T3a-T3d were 550, 420, 55, and 48 kDa, respectively. Glycosidic linkage analysis showed that they had a mannan backbone consisting of 3-linked Man p, and side chains containing glucosyl, mannosyl, fucosyl, xylosyl, and glucuronic acid residues attached through O-2, O-4, or O-6 of about half of the backbone mannosyl residues. A partial acidic hydrolysate of T3a could be divided into a low-branching region (T3a-1, 2, 3, 4) mainly branched at the 2-position of 3-linked Man p in the mannan backbone, and a high-branching region (T3a-5A) branched at the 2,4- or 2,4,6-positions of 3-linked Man p in the backbone. The low-branching region, which is predominant in the backbone, was substituted with non-reducing terminal Glc pA, Fuc p and short side chains consisting of (1-->6)-linked Glc p and (1-->2)-linked Man p linked through C-2 of the mannan backbone. The high-branching region, which is a minor component of the backbone, was linked with long side chains of (1-->6)-linked Glc p and (1-->4)-linked Glc pA in their branching points. T3a-T3d were able to induce human monocytes to produce interleukin-1, interleukin-6, and tumor necrosis factor in vitro. The different fragments of the acidic hydrolysate of T3a (T3a-1, 2, 3, 4, 5A) also induced monocytes to secret interleukin-6 with high potency, indicating that the activity may be caused by a common structure, (1-->3)-mannan in the four heteroglycans and their fragments. The change of molecular weight had no obvious influence on the activity of the heteroglycans.