Clinical lines of evidence have been accumulated that hepatitis B virus (HBV) genotypes have characteristic geographical distributions and distinct clinical impact on liver diseases. The distribution of HBV genotypes was determined with reference to hepatitis B e antigen (HBeAg) and alanine aminotransferase (ALT) levels in 165 patients with hepatitis B in San Francisco. HBV genotypes were determined by enzyme-linked immunosorbent assay (ELISA) and the unclassified samples were sequenced within the S region for phylogenetic analysis. Genotype A occurred in 60 (36%) patients, B in 16 (10%), C in 56 (34%), D in 19 (12%), E in 1 (1%), F in 1 (1%), G in 8 (5%), and H in 4 (2%). Caucasians were infected predominantly with HBV genotype A (HBV/A) (38 of 57 [67%]), Asians with HBV/C (45 of 63 [71%]), and Hispanics with HBV/F and HBV/H (4 of 9 [44%]). Serum ALT levels were higher in the patients infected with HBV/A (P = 0.03) or HBV/G (P = 0.02) than HBV/C. HBeAg was more frequent in patients infected with HBV/G than HBV/C or HBV/D (7 of 8 [88%] vs. 25 of 56 [45%] or 6 of 19 [32%], P = 0.03 or 0.01). In conclusion, eight genotypes (A-H) were identified in San Francisco in association with various ethnicities and then influenced ALT levels as well as the prevalence of serum HBeAg. HBV genotype H might be identified by combination of preS2 serotpe bksf and HBsAg serotype adw.