The fiber genes of human adenovirus types 8, 9, 15, and two genome types of intermediate adenovirus 15/H9, all belonging to subgenus D, were sequenced and the nucleotide and predicted amino acid sequences compared. The analyzed peptide sequences were consistent with the structural domains described for other adenoviruses: an amino-terminal tail region, an intervening shaft region composed of eight repeating 15-amino-acid segments, and a carboxy-terminal knob. Furthermore, several highly conserved sequences could be confirmed. The fiber genes of AV9 and the AV15/H9 intermediate strains were 100% identical, not only in the coding region, but also in the presented 5'- and 3'-flanking regions. These findings support the hypothesis that intermediate strains arise by recombination of two serologically different parent viruses. The predicted AV8, AV9, and AV15/H9 polypeptides showed an overall homology of 92%. In the knob regions, AV8 and AV9; AV15/H9 intermediate strains revealed nine mismatches. AV8 is the main causative agent of epidemic keratoconjunctivitis in man, whereas AV9 and the AV15/H9 intermediate strains only infrequently cause acute follicular conjunctivitis. Since the knob is the component responsible for interaction with the cell receptor, these differences in the receptor binding sites should be expected to play an important role in the differences in pathogenicity.