The purpose of this study was to assess prognostic factors and survival in patients with liver involvement in immunoglobulin light-chain amyloidosis. Comparisons were made with other patients with immunoglobulin light-chain amyloidosis who did not have liver involvement. A total of 77 consecutively seen patients were evaluated: 19 had hepatic amyloidosis and 58 had amyloidosis without liver involvement. Eighteen of 19 patients with liver amyloidosis could be histologically diagnosed without needle biopsy of the liver. All but 2 had a detectable free light chain in the serum or urine, distinguishing this from other infiltrative liver processes. Patients with liver amyloid had significantly higher alkaline phosphatase levels and C-reactive protein levels compared with patients without hepatic amyloid. The majority of patients had extrahepatic involvement predominantly in the kidney (47%) or heart (42%). The presence of hyposplenism was not a good screening test for the presence of hepatic amyloid. Seven of 19 patients responded to chemotherapy with objective regressions of the clinical manifestations of renal, hepatic, or cardiac involvement. We conclude that the survival of patients with liver involvement in amyloidosis is no different than other patients with amyloidosis. This results from the high proportion of patients having associated renal or cardiac involvement. Most patients can be diagnosed without a liver biopsy when a monoclonal protein is found in the serum or urine. Serum albumin and C-reactive protein levels appear to distinguish patients with liver involvement from those without.