The possibility that the disturbed immunity associated with primary biliary cirrhosis (PBC) includes abnormal metabolism of the complement system was investigated by conducting simultaneous studies of the turnover of highly purified, hemolytically active, 125I-labeled C3 (3rd component of complement) and 131I-albumin in 7 control subjects and 9 patients with PBC. Aliquots of each 125I-C3 preparation were injected, together with 131I-albumin, into 1 or 2 normal subjects and 1-3 patients with PBC and plasma and urine radioactivity data were analyzed. In all patients with PBC, disappearance of 125I from plasma was much more rapid than in controls. In 5 of these patients, no terminal monoexponential decline of 125I occurred. The mean fractional catabolic rate (FCR) of C3 was higher in PBC (4.23 .+-. 0.32% [standard error of the mean] IV pool/h) than in controls (2.02 .+-. 0.08% IV pool/h, P < 0.0005). In contrast, the mean FCR of albumin was similar in PBC (11.4 .+-. 1.29% IV pool/day) and controls (11.5 .+-. 0.76% IV pool/day), suggesting that the increased FCR of C3 in PBC was not due to a nonspecific process. There was no correlation between values for the FCR of C3 and indices of cholestasis. The mean synthetic rate of C3 was higher in PBC (2.94 .+-. 0.48 mg/kg per h) than in controls (1.03 .+-. 0.11 mg/kg per h, P < 0.0025). In 5 patients, relatively more C3 was extravascular than in controls. The results are consistent with PBC being associated with chronic activation of the complement system and increased tissue attachment of C3, phenomena which could be related to a process of pathogenic significance in this disease.