A B S T R A C T To assess the role ofcirculating immune complexes in the pathogenesis of acute rejection, sera were measured for such complexes by the 125I-Clq binding assay in 45 normal subjects, 24 allografted patients undergoing acute rejection, and in 11 allografted patients in a quiescent phase. Increased Clqbinding activity (Clq-BA) was detected in 14 patients with acute rejection, 9 of whom had renal biopsies showing fibrin deposition in the vasculature together with cellular infiltrates in the tubulo-interstitial structures; renal histology was not available in the other 5 patients. The other 10 patients with acute rejection, whose biopsies showed only cellular infiltrates, and the 11 patients in a quiescent phase posttransplantation did not have increased levels of serum Clq-BA.Of the group with increased serum Clq-BA, serial studies in eight patients showed a correlation between increased serum Clq-BA and the occurrence of rejection; with reversal by therapy, serum Clq-BA returned to within normal levels. Complexes from six patients were analyzed by sucrose density gradient ultracentrifugation to have sedimentation coefficients ranging from 15S to 18.4S. After acid dissociation and analysis by double-diffusion techniques, Clq-reactive complexes were shown to contain IgG. Immunofluorescent studies done in five renal biopsies from this group revealed granular deposits of immunoThis work has been previously published in abstract form: 1976. Kidney Int. 10: 608. (Abstr.)