We used an anchor polymerase chain reaction method to compare the repertoires of transcribed T-cell receptor beta chain variable region (V beta) genes in cord blood T cells from neonates of hepatitis B surface antigen (HBsAg) positive (n = 40) and HBsAg negative (n = 40) women. Fifteen of the HBsAg positive women were hepatitis B e antigen (HBeAg) positive, and 25 were HBeAg negative. The percentage of V beta 7.4 transcripts was lower in cord blood T cells from neonates of HBsAg-positive relative to HBsAg-negative women (9.7% +/- 0.5% vs. 12.7% +/- 0.6%, P = .002). The percent of V beta 5.1 transcripts was higher in cord blood T cells from neonates of HBeAg-positive relative to HBeAg-negative women (9.3% +/- 0.7% vs. 7.0% +/- 0.3%, P < .001). There were no correlations between neonatal maturity at birth and V beta repertoire. In summary, a maternal chronic hepatitis B virus (HBV) infection is associated with changes in the repertoire of transcribed T-cell receptor genes in neonatal cord blood T cells. It is possible that the T-cell response to the HBV is associated with a limited repertoire of V beta genes. The mechanism of vertical chronic HBV infection in human neonates may involve changes in the T-cell response to the virus that are induced in utero.