Based on the analysis of HDV genomes from different areas of the world, three genotypes of HDV have been identified. Genotype I is the most prevalent and widespread. Genotype II is represented by two isolates from Japan and Taiwan. Genotype III has been found only in the Amazonian basin where it is associated with a history of severe disease, fulminant hepatitis with microvesicular steatosis (spongiocytosis). We report here the cloning and the analysis of the complete viral genome from woodchuck serum-derived HDV RNA after transmission from Central African Republic (RCA) patients with fulminant spongiocytic delta hepatitis. Two overlapping cDNA fragments, covering the entire HDV genome, were generated by RT-PCR and cloned. Three clones obtained from each fragment were fully sequenced. A complete consensus RCA HDV genome was reconstituted. The individual and the consensus nucleotide sequences were compared with those of 16 other fully sequenced isolates belonging to the three genotypes. Phylogenetic trees generated by the neighbour joining method firmly place our isolate in genotype I, and show that this RCA isolate differs significantly from the east African isolates previously analysed. Transfection experiments showed that the isolate is replication-competent, but less so than the control "wild-type" strain. Two novel mutations encountered in this work, one in the antigenomic ribozyme sequence and one affecting delta antigen, were studied.