In 32 patients with a renal allograft, serial determinations after transplantation were made of C3d, the stable conversion product of the complement factor C3, as well as serial measurements of the anaphylatoxin C3a des arg. Furthermore, serial determinations were made on the presence of circulating immune complexes using three different assays (C1q binding assay, polyethylene glycol precipitation test, and indirect granulocyte phagocytosis test). Twenty patients were studied during an active cytomegalovirus (CMV) infection, and 12 patients were studied during allograft rejection or during stable phase after renal transplantation. In 12 patients with a CMV infection serial measurements were made of AP50 (alternative pathway of complement). During an active CMV infection elevated C3d as well as elevated C3a des arg levels were found and not in the control group (P less than 0.01). In 8 out of the 12 patients tested, with CMV infection, a decreased hemolytic activity of the alternative pathway (AP50) was found, together with the elevated levels of C3d and C3a des arg. Serum C4 levels were normal or high during CMV infection. Furthermore, circulating immune complexes were found to be positive in 15 out of the 20 patients with a CMV infection (both primary and secondary infections), and in 2 out of 12 patients of the control group. The complement activation found in the CMV group was not related to the presence of circulating immune complex-like material, since complement activation was present in advance of the appearance of the immune complexes, suggesting that complement activation was not due to classical pathway activation by those complexes. We conclude that our data are consistent with complement activation and the formation of biologically active peptides like C3a des arg in patients with an active CMV infection. The decreased hemolytic activity of the alternative pathway (AP50) together with the normal or high C4 levels suggest involvement of the alternative pathway, although further studies of the alternative pathway of C are warranted to confirm this hypothesis.