Reports on the generation and nephritogenic capacity of posttransplant circulating immune complexes (CIC) are conflicting. To assess the pathogenicity of CIC in acute rejection (AR), 784 CIC determinations were performed on 392 serum samples from 27 [human] pediatric renal allograft recipients using the C1q-solid phase assay and the Raji cell [human Burkitt''s lymphoma] radio immunoassay. Serum samples from transplant recipients not undergoing rejection episodes and from normal subjects served as controls. Of the 784 CIC determinations, 723 (92.3%) were negative in both assays. CIC were present at some point posttransplant in 8 (19.6%) recipients. Correlation of CIC levels with allograft rejection was found in only 2 patients with CIC levels responding to antirejection therapy; statistical analysis of data by .chi.2 analysis failed to reveal a significant correlation of CIC with AR episodes. Allograft histology in 3 recipients demonstrated characteristic AR signs. Immunofluorescent studies did not reveal significant deposition of Ig or complement. Sucrose density gradient ultracentrifugation studies confirmed the immune complex nature of materials reactive with the CIC assays. There was no immunological evidence supporting antithymocyte globulin as an immunogen in patients demonstrating CIC posttransplant. CIC do not appear to be an important AR mediator. Statistical analysis of data using the .chi.2 test failed to reveal a positive correlation of CIC levels with AR or ultimate allograft outcome.