Considerable knowledge has been accumulated regarding the characteristics of acute post-streptococcal glomerulonephritis (APSGN), and many attempts have been made to identify a streptococcal factor or factors responsible for triggering this disease. However, the pathogenic mechanism behind APSGN remains largely unknown. As glomerular deposition of C3 is generally demonstrated before that of IgG in the disease process, it is likely that the inflammatory response is initiated by renal deposition of a streptococcal product, rather than by deposition of antibodies or pre-formed immune complexes. During recent years, a number of streptococcal products have been suggested to be involved in the pathogenic process. In this review, possible roles of these factors are discussed in the context of the clinical and renal findings most often demonstrated in patients with APSGN. Streptokinase was observed to be required in order to induce signs of APSGN in mice, and a number of findings suggest that the initiation of the disease may occur as a result of renal binding by certain nephritis-associated variants of this protein. However, additional factors may be required for the development of the disease.