In Thailand, chronic liver disease (CLD) as a consequence of infection with hepatitis B virus (HBV) constitutes a public-health burden. Control and treatment are complicated by the virus exhibiting an unusually high mutation rate, with some genotypes apparently causing more severe disease than others. Restriction-fragment-length-polymorphism (RFLP) analysis of the pre-S region of the viral genome, amplified by PCR, was used to determine which genotypes were most prevalent among Thai patients chronically infected with the virus. The patients were chronic HBV carriers (40) or cases of chronic hepatitis (34), cirrhosis (14) or hepatocellular carcinoma (30). As indicated by the results of earlier studies on CLD patients in South-east Asia, genotype C (68.6%) was clearly predominant. RFLP patterns permitted the C1 (12.7%), C7 (45.7%), C8 (10.2%) and B1 (29.7%) subtypes to be identified. Two samples that could not be typed by RFLP were analysed by direct sequencing, categorized as type C, and tentatively designated as subtype C9. As comparison of the present data with those previously obtained by direct sequencing of PCR products indicates that RFLP analysis is as specific and reliable as sequencing and less expensive and time-consuming, RFLP analysis may be particularly useful for epidemiological studies.