We have previously shown a significant increase in sulfate-35 uptake in rat glomerular basement membrane (GBM) when glomeruli were cultured with peripheral blood mononuclear cells (PBMC) from patients with idiopathic minimal lesion nephrotic syndrome (IMLNS) in relapse. In the present study, we have isolated the lymphokine mediating the augmented sulfate-35 incorporation and evaluated its effect on the catabolism of the GBM sulfated compounds. Supernatants from IMLNS PBMC cultures of 13 patients in relapse and 10 in remission were fractionated using gel filtration chromatography. There was a significant increase in rat GBM sulfate-35 uptake when glomeruli were cultured in carbonic anhydrase fraction from patients in relapse (12.9 ± 3.2; cpm/μg GBM protein, mean ± SEM) as compared to glomeruli cultured in the same fraction from patients in remission (8.2 ± 2.5: cpm/μg GBM protein; p < 0.05). The catabolism of the GBM sulfated compounds was determined by studying the washout of the sulfate-35 macromolecules after equilibration in sulfated isotope-free medium for 12 h. There was a significant decrease in residual sulfate-35 in rat GBM when glomeruli were cultured in a 29-kD fraction from patients in relapse (7.0 ± 2.5; cpm/μg GBM protein, mean ± SEM) as compared to glomeruli cultured in the same fraction from patients in remission (31.8 ± 1.6; p < 0.005). No significant differences in sulfate-35 incorporation were seen when other fractions from patients in relapse and in remission were compared. These studies suggest that the lymphokine secreted by PBMC from IMLNS patients in relapse increases the catabolism of the GBM sulfated compounds. This may cause a decrease in GBM net negative charge resulting in increased glomerular permeability to plasma