Changes in serum alpha-fetoprotein (alpha FP) 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 alpha FP levels in controls were found to be always lower than 5 ng/ml (0.1-4.4 ng/ml, mean +/- 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 alpha FP 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 alpha FP levels (76.7, 122.8, and 1,600 ng/ml at entry): alpha FP 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 alpha FP levels in HBeAg-positive patients were significantly higher than in HBeAg-negative patients both at entry and during the follow-up (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)