Antibodies to liver cytosol antigen type 1 (anti-LCl), which recognize a 60-kd peptide contained in the liver cytosolic fraction, have been reported to define a subset of autoimmune hepatitis (AIH) either negative for other autoantibodies or positive for anti-liver kidney micro-soma1 antibody type 1 (LKM-1) and to be best detected in immunodiffusion. To analyze the prevalence of anti-LC1 in childhood liver disease, we have tested the sera of 95 patients using immunoblot, indirect immunofluorescence, and immunodiffusion. Fifteen children had smooth muscle antibody (SMA) andor anti-nuclear antibody (MA)-positive AM, 13 had anti-LKM-1-positive AIH, 14 had autoimmune sclerosing cholangitis (ASC) (all SMA andor ANA positive), and 53 had non-autoimmune liver disease (10 had al-anti-trypsin deficiency [al-ATD], 11 had Wilson's disease [WD], 14 had Alagille's syndrome, and 18 had chronic hepatitis B virus [HBV] infection). Twenty healthy children were studied as controls. Anti-LC1 positivity in immunodiffusion and strong reactivity in immunoblot were found in 4 LKM-1and 2 SWANA-positive patients with AIH and in 1 patient with ASC, but in none of the patients with other liver diseases nor in controls. A weak 60-kd band was detected by immunoblot in 6 more patients with AIH (2 were LKM-1and 4 were SWANA-positive) and 6 patients with ASC, all anti-LCl-negative by immunofluorescence and immunodiffusion. No distinct clinical features characterized the anti-LCl-positive patients. Our data show that, in pediatric age, LC1 reactivity, although associated with autoimmune liver disease, does not identify a distinct disease subset and that immunoblot is the most