The serum kinetics of preS1 and preS2 antigens has been evaluated in 38 serial samples from eight patients with chronic active (CAH) or chronic persistent (CPH) hepatitis, followed for 2-7 years (mean 4.4 years) in whom liver biopsy was performed at intervals, and in 46 samples from ten asymptomatic HBsAg carriers followed for 4-5 years (mean 4.6 years). Four patterns of preS behaviour have been observed: (1) persistently positive preS1 and preS2; (2) disappearance of preS2; (3) disappearance of both preS1 and preS2; and (4) persistently negative preS1 and preS2. Pattern 4 has been observed exclusively among healthy carriers, while seven out of eight chronic patients exhibited either pattern 1 or 2. Among the chronic patients, preS2 disappearance was accompanied or followed by alanine aminotransferase (ALT) normalization. The correlation of preS antigens with conventional viral replication markers showed that 100% of hepatitis B virus (HBV)-DNA-positive and 86.6% of HBeAg-positive sera were preS1/preS2 positive, while 61% of HBV-DNA-negative and 64% of HBeAg-negative sera were preS1/preS2 negative. Our data suggest that continuous monitoring of preS antigens in follow-up sera will allow for an improved prognostic evaluation of chronic HBV infection.