We investigated the effect of excess complement factor D on the immune complex solubilization activity (ICSA) of serum. First, we estimated the concentration of factor D, ICSA and the hemolytic activity via the classical complement pathway (CH50) in the sera of 16 healthy individuals and 36 patients on hemodialysis for end-stage renal failure. The serum concentration of factor D in these patients (mean ± SD: 12.12 ± 2.38 μg/ml) was significantly higher (p < 0.001) than that in the healthy subjects (1.02 ± 0.11 μg/ml). In this study, peroxidase and antiperoxidase rabbit IgG were used as immune precipitates for ICSA. The ICSA in patients (45.8 ± 7.4 normal human serum %, NHS%) was significantly lower (p < 0.001) than that in the healthy subjects (100.2 ± 12.5 NHS%). There was no difference in CH50 between the sera of the patients (31.8 ± 2.5) and that of the healthy group (32.4 ± 2.6). Second, we determined that increasing amounts of purified factor D added to fresh serum resulted in a decrease in ICSA. This occurred in the serum of a healthy individual as well as in that of a patient. CH50 did not change regardless of the concentration of factor D used. There was an increase in C3 conversion in the sera to which purified factor D had been added, as observed by crossed immunoelectrophoresis. It is suggested that ICSA had deteriorated due to the excess of factor D, which had activated the alternative pathway of complement.