The activation of the complement system by phenolic glycolipid 1 (PGL) from Mycobacterium leprae was studied. It was found that PGL consumed haemolytic complement through both the classical and the alternative pathways. This was further studied at the level of C3. Although the activation was independent of anti-PGL antibodies present in normal human serum, the addition of antibody augmented the activation of complement by PGL. The uptake of C3 through the classical pathway was enhanced predominantly by IgM antibody whereas, IgG antibody against PGL was responsible for the augmentation of the alternative pathway activation. Furthermore, it was found that both the disaccharide and trisaccharide components of PGL were able to activate the complement system. © 1990.