Increased complexing of circulating group-specific component (Gc, vitamin D-binding protein) has been found in humans under conditions of presumed increased actin release, and particularly fulminant hepatic necrosis (FHN). We therefore used a hamster model of acetaminophen-induced FHN to further investigate this phenomenon. Liver damage was monitored by aspartate aminotransferase (AST) activity and by histologic examination, and serum Gc was analyzed by polyacrylamide gel electrophoresis (PAGE) and transblotting with anti-Gc. In controls and treated animals displaying slight liver damage, greater than 90% of Gc was of mobility corresponding to native purified hamster Gc, whereas with more severe liver damage up to 100% of Gc was found in one of two cathodal configurations that appear to correspond to complexes with actin. Densitometric quantitation of complexed Gc demonstrated a strong correlation with the severity of liver damage. These results show PAGE to be a useful method of estimating the percentage of Gc complexed in serum, and suggest that cell damage may be followed by the appearance in the circulation of cellular actin that complexes with Gc.