Activation of the alternative complement pathway (AP) has been investigated in 79 serial serum samples obtained from 28 patients which had different types of glomerulonephritis. Serum factors activating the AP of the complement system have been detected in 12 patients with various forms of glomerulonephritis. Immune complexes (IC), levels of complement components of the classical and the alternative pathways and cobra venom factor activity were measured. Serum specimens were subcategorized as 2 study populations: (i) patients with serum factors activating AP and (ii) patients with both serum activators and IC. Although CoVF-AH50, properdin factor B and C3 concentrations were comparably depressed in these two groups, the levels of C1q and C4 were very low only in patients with circulating IC. These data were highly suggestive of AP activation due to serum factor. In contrast the patients also showing circulating IC had activation of both pathways. The presence of these factors suggests that renal damage can be determined by other immunological stimuli.