The purpose of this study was to investigate which structures of the nephron, if any, are capable of directly activating the complement (C) system. To this end, two sets of experiments were performed. First, activation of C was assessed on sections of frozen kidney tissue, using the indirect immunofluorescence technique for the demonstration of C fixation. Second, glomerular or tubular fractions of kidney were incubated with normal fresh serum, and subsequent C consumption was measured. The data obtained support the interpretation that the brush border of proximal tubules activates the alternative pathway of the C system. This phenomenon may have pathogenic significance in conditions of aselective proteinuria.