A radioimmunoassay for serum procollagen III aminopeptide (sPIIIP) was proposed recently for monitoring hepatic fibroplasia in patients with various inflammatory hepatic lesions. To determine whether sPIIIP also can detect fibroplasia in noninflammatory liver disorders, we measured this index in 16 patients with idiopathic hemochromatosis (IHC) at various stages of the disease and iron overload. Interestingly, we found normal levels of sPIIIP in 12 out of 16 patients examined (75%), despite clear histologic features of fibrosis or cirrhosis. The levels of sPIIIP exhibited no relationship to any of the clinical, laboratory, or histologic parameters of the disease. Thus, unlike other types of cirrhosis, in which sPIIIP is increased, the liver disease in IHC may be a fibrotic process unrelated to type III collagen stimulation. Accordingly, the determination of sPIIIP in these patients is of no value for monitoring the fibrosis associated with the liver disease.