The drug, pentosan-poly-sulfoester (PPS), has an anticomplementary activity (ACA) on human serum both in vitro and in vivo, as judged by a reduction in total hemolytic complement activity (CH 50). In vitro, this ACA is very potent, immediate and temperature independent. In vivo, this ACA obtained with a i.v. dose of 100 mg/8 h, e.g., 300 mg/24 h, increases with the duration of treatment (mean time: 30 days), suggesting a cumulative effect. Eleven patients with glomerulonephritis (GN) received such a treatment (8 with acute post-streptococcal GN and 3 with mesangio-proliferative GN). In patients with already marked hypocomplementemia, the ACA is difficult to establish, while in patients with normal complement activity or moderate hypocomplementemia, the decrease of CH 50 level in serum is obvious. There was no significant change in the serum level of C[complement]3, C4, properdin factor B as measured by radial immunodiffusion technique. The clinical course of these GN was apparently not affected by this treatment. The in vivo ACA of PPS is firmly established and it is speculated that this functional depletion in complement may prevent or decrease the liberation of humoral mediators of inflammation.