The relationship of basement membrane to interstitial collagen-related protein metabolism was investigated in a sample of 100 consecutive patients undergoing surgery for gallstone disease. The measurements were performed on both sera and bile specimens using specific radioimmunoassays for type IV collagen, laminin, endogenous intact human type III collagen aminopropeptide and its degradation product, Col. 1. While basement membrane related proteins, type IV collagen and laminin were dominant in the bile, type III collagen related proteins were lower than in the corresponding serum samples. Both the intact type III procollagen peptide and its Col. 1 fragment were, however, found in the bile. The highest bile laminin concentrations were observed in patients with gallbladder fibrosis, whereas type III aminopropeptides were elevated not only in fibrosis and cancer but, most markedly, in acute inflammation of the gallbladder. Bile type IV collagen concentration was also found to vary according to the cholesterol content of gallstones. The results point to differences in the metabolism of various extracellular matrix proteins during the development of gallstone disease. The association between such proteins, the histological alterations in the gallbladder wall and the cholesterol content of gallstones may have implications for the pathogenesis of gallstone disease.