The impact of aging on the severity of chronic immune-complex glomerulonephritis was studied in 144 patients from whom diagnostic renal biopsies were obtained over a 3-year period. Glomerulonephritis was related to an antecedent streptococcal infection in nine of these patients. In 58, glomerulonephritis occurred in association with a systemic disease; 27 of these had lupus erythematosus. At the time of the renal biopsy, serum creatinines were more frequently abnormal in men over 40 years of age. Similarly, histological evidence of irreversible glomerular injury was more evident in men over 40. Histological indices of renal glomerular injury correlated with the presence of intense fluorescent antibody reactions specific for C3 and C4 and IgG in the glomeruli. High serum Clq binding activities (Clq BA), an indication of the presence of circulating immune complexes, also were found significantly more often in males over 40. High serum Clq BA correlated with renal functional and biopsy evidence of severe glomerulonephritis. The renal biopsies in 89 cases were tested with fluorescein-conjugated heat-aggregated IgG (FAIgG) to determine how many contained focal immunoglobulin deposits with antiglobulin activity. Antiglobulins were detected in glomeruli of 24 patients and were found significantly more often in biopsies which revealed histological evidence of severe and irreversible histological injury. Binding of FAIgG was not selectively associated with any sex or age groups. Thus, detection of circulating immune complex-like materials in sera and the presence of glomerular deposits with antiglobulin activity were both features associated with severe glomerular injury. Both correlated with the quantity of complement deposited in the glomeruli. But only serum Clq binding activity was age and sex related. Similarly, in cancer patients, abnormal Clq BA were found more frequently in sera of older men with cancer but not in age- and sex-matched controls. Examination of selected sera by sucrose density gradient ultracentrifugation revealed that the complexes from cancer patients were relatively small (less than 19S greater than 7S) whereas those in most nephritis patients were heterogeneous in size. Sera with relatively high Clq binding activity from patients with chronic glomerulonephritis tended to contain relatively greater quantities of Clq binding materials sedimenting more rapidly than 19S.