Using C1q binding, Kg binding, and Raji cell radioimmunoassays, the relationship between renal allograft rejection and the circulating immune complexes was examined in 90 patients with renal transplants. The data showed that there was a significant quantitative correlation between C1q-binding and Raji-cell-binding activities (Rs = 0.53, P less than 0.001), and that both activities were closely associated with the occurrence of chronic rejection (chi 2 = 45.9-34.1, P less than 0.001). On the other hand, Kg-binding activities were not correlated with C1q-binding or Raji-cell-binding activity (Rs = 0.07-0.17, P greater than 0.1) and a close association was observed with acute rejection episodes (chi 2 = 11.5, P less than 0.001). The results of sucrose density gradient analysis were in keeping with previous findings in that the individual assays detect immune complexes of different compositions: the Raji cell test was shown to measure not only immune complexes but also monomeric IgG. Immunofluorescent studies of the transplant kidney specimens showed that the majority of patients in a state of chronic rejection had glomerular deposits of immunoglobulins and complement--in contrast to negative findings in patients without rejection episodes. All these data indicate that several tests for immune complexes are more informative than the single test for monitoring rejection, and suggest that the appearance of circulating immune complexes after renal allografting is related to the rejection phenomenon.