In order to elucidate their role in mediating renal immune injury in man, the glomerular C3b receptors have been analyzed in frozen sections of 205 kidneys biopsied from 199 patients affected by various well-defined renal diseases. Using fluoresceinated C3b-coated bacteria as the indicator system, the receptor activity has been compared with that found in 10 normal human kidneys. In 76 out of 98 cases (77%) of glomerulonephritis (GN) with capillary wall abnormalities, a significant loss of receptor activity has been observed. No difference was present between the 89 patients affected by GN presumably due to immune complexes (ICX) parietal deposition (membranoproliferative, membranous, acute poststreptococcal GN and proliferative GN of SLE and cryoglobulinemia) and the 9 patients affected by GN presumably due to anti-GBM antibodies (Goodpasture’s syndrome and extracapillary GN). In the group of ICX-GN, no correlation could be demonstrated between inhibition of C3b receptors and the presence of parietal C3 deposits. A significant loss of receptors activity has been also demonstrated in 12 out of 13 patients with amyloidosis or diabetic glomerulosclerosis. On the contrary, inhibition of C3b receptors has been observed in only 3 out of 20 patients with nonglomerular renal diseases (interstitial and vascular nephropathies) and in only 11 out of 57 patients (19%) affected by mesangial GN with no capillary wall abnormalities (Berger’s disease, Henoch-Schonlein purpura and mesangial GN of SLE). C3b receptors were normal in 13 out of 17 patients affected by lipoid nephrosis (minimal change GN or focal glomerulosclerosis). In conclusion, the analysis of C3b receptors in renal diseases do not support the hypothesis of their involvement in parietal localization of C3b-bearing ICX: these results rather suggest that the receptors become undetectable in many glomerular diseases (immune-mediated or not) with lesions of capillary walls, because of the loss of integrity of C3b receptor-bearing visceral epithelial cells.