Changes in serum α-fetoprotein (αFP) levels were investigated by radioimmunoassay during the follow-up (17 ± 12 months, two to three times per year) of 50 children with chronic hepatitis B virus infection (mean age of 8 years, 30 males) and of 35 healthy age- and sex-matched controls. Eleven of 50 were healthy carriers; 7 had chronic persistent hepatitis, 29 had chronic active hepatitis, and 3 had cirrhosis-associated chronic active hepatitis. Serum αFP levels in controls were found to be always lower than 5 ng/ml (0.1–4.4 ng/ml, x ± SD of 1.34 ± 1.32 ng/ml). Statistical analysis after logarithmic transformation showed a significant difference between mean levels (ng/ml) in controls and in patients [geometric mean = 0.83 C.L. (95% confidence limits of 1.19/0.58) vs. 3.43 (95% C.L. of 4.79/2.45);p= 0.0001]. Mean values of serum αFP levels at entry were higher than those found at the end of the follow-up period [geometric mean = 3 (95% C.L. of 4.69/1.92) vs. 1.48 (95% C.L. of 2.13/0.95);p= 0.038]. Only three patients repeatedly showed high αFP levels (76.7, 122.8, and 1,600 ng/ml at entry): αFP values became normal after a mean follow-up of 17 ± 7.8 months as well as liver enzymes, with no changes in serum “e” antigen-antibody and anti-delta antibody status being observed. Mean values of serum αFP levels in HBeAg-positive patients were significantly higher than in HBeAg-negative patients both at entry and during the follow-up (p= 0.05). Serum logarithmic αFP values were significantly correlated with log aminotransferases (alanine aminotransferase:r= 0.38 andp< 0.0001; aspartate aminotransferase:r= 0.36 andp< 0.0001) and log γ-glutamyl transpeptidase (r= 0.32 andp< 0.0001). Although serum αFP levels were found to be higher in patients with the most severe histological damage, they did not allow the accurate discrimination of histological categories in individual patients.