By combining the polymerase chain reaction (PCR) with restriction enzyme digestion technologies, we characterized the genomes for the small and large delta proteins of HDV in retrospective analysis of sera from 10 patients with varied clinical outcomes. Both small and large genomes of HDV were present in all 13 serum samples from the 6 acute and 4 chronic cases studied, while the specific HDV proteins (P24 and P27) could be detected by immunoblot analysis in only 4 of them. The relative amounts and ratios of the genomes for the large and the small proteins of HDV were different for each individual. The molecular ratio of large to small HDV genomes in serum correlated with viral replication. When the replication of HDV RNA increased, the ratio decreased and vice-versa. No specific correlation, however, was found between the ratio of both molecular forms and the clinical outcome.