Abstract Normal rats were injected with guinea pig anti-rat glomerular basement membrane antibodies of the IgG1 or IgG2 class or with their F(ab′)2 fragment, in order to study which antibody site triggers the alternate complement pathway in vivo. Both IgG classes were able to induce a heavy proteinuria and led to C3 deposition in the glomeruli in a pattern similar to their own distribution along the glomerular basement membrane, as shown by the immunofluorescence technique. The Fab(ab′)2 fragment of IgG2 did not produce C3 binding or proteinuria. The F(ab′)2 fragment of IgG1 was difficult to obtain devoid of Fc determinants. A F(ab′)2 fragment of IgG1 still bearing Fc determinants led to C3 binding and proteinuria, whereas the true F(ab′)2 fragment of IgG1 had none of these effects in two out of three animals.