The degradation of the heparan sulfate proteoglycans of subendothelial matrix by neutrophil elastase and the myeloperoxidase-H2O2-chloride system added separately, sequentially, or together at pH 4.5 to 7.5 was determined by the release of lower molecular weight 35S-labeled material. Elastase alone and the myeloperoxidase system alone caused degradation, and when 4-hour exposure to elastase was followed by 15 minutes of exposure to the myeloperoxidase system, the effect was greater than additive. A greater than additive effect was not observed when elastase followed the myeloperoxidase system or the two were added together. Chloride (or sulfate) alone increased the release of 35S-labeled material from elastase-treated matrix, although the effect of 0.1 M chloride was not as great as that observed when an equivalent concentration of chloride was combined with myeloperoxidase and H2O2. The release of these systems at sites of adherence of neutrophils to glomerular basement membrane may contribute to neutrophil-associated proteinuria.