Monomeric G-actin has recently been shown to form high-affinity complexes with group-specific component protein (Gc), and this process might be expected to occur in vivo when hepatocyte necrosis with release of actin takes place. We therefore measured serum Gc levels and searched for evidence of actin-containing complexes of Gc in 147 sera from 21 normal subjects and 126 patients with acute and chronic liver diseases. Sera were examined for Gc concentration using an ELISA with purified Gc as standard. Gc levels were greatly diminished (less than 10 mg per dl) in 5 of 37 patients with acute hepatitis and 1 of 3 patients with subacute hepatic necrosis, and the mean values for these groups overall as well as those for chronic active hepatitis patients were significantly less than that observed in the normal controls (mean, 35.5 mg per dl). No significant alteration in Gc level was observed in the chronic disease categories studied. In contrast, Gc concentrations less than 10 mg per dl were found in 12 of 14 patients with fulminant hepatic necrosis, and the mean for this group (9.7) was significantly reduced (p less than 0.001). Sequential studies in 12 patients with acute hepatitis of moderate to marked severity but without a fulminant phase showed significant diminutions in initial Gc levels when these were compared with Gc levels obtained during recovery. Using analytical isoelectric focusing with print immunofixation, variable amounts of Gc:G-actin complexes could be demonstrated in virtually all sera examined, but the proportion of total Gc present as complex with G-actin appeared greater in fulminant hepatic necrosis sera.(ABSTRACT TRUNCATED AT 250 WORDS)