Endostreptosin (ESS) is an immunologically well defined cytoplasmic antigen of group A and some group C streptococci. ESS is probably the pathogenetic antigen of poststreptococcal glomerulonephritis (ASGN). Antibodies to ESS (ESS-Ab) were determined by microcomplement fixation in 1,102 patients and by ELISA in 105 patients. In 168 patients with ASGN (90 from the U.S.A. and 78 from Kuwait) the arithmetic mean titer was 45.2 (log10 1.40 +/- 0.606) and 50.2 (log10 1.51 +/- 0.394) respectively, both significantly elevated compared to 347 age matched children and adults from the U.S.A. whose arithmetic mean titer was 9.1 (log10 0.83 +/- 0.635) and 7.5 (log10 0.55 +/- 0.492) respectively and 139 children from Kuwait whose arithmetic mean titer was 15.7 (log10 0.92 +/- 0.495). In 51 patients with ASGN, the mean ELISA value was 67.5% higher than the values obtained from 54 normal age matched controls. Patients with streptococcal infections without renal involvement had only transiently and mildly elevated values. ESS-Abs in patients with other types of glomerulonephritides were in the range of normal. ESS-Ab titers do not parallel the titers of streptococcal exoenzymes. ESS-Ab titers are of importance for the differential diagnosis of renal diseases and of similar significance for the understanding of the pathogenetic mechanism of ASGN. They are possibly of significance for therapy in the form of an active vaccine.