A total of 8 different genome types of adenovirus type 4 (Ad 4), Ad 4p, Ad 4p 1-3, Ad 4a, Ad 4a 1, Ad 4b, and Ad 4ch were identified among 50 selected human adenovirus isolates and 2 chimpanzee adenovirus strains using 16 restriction endonucleases Bam HI, Bcl I, Bgl I, Bgl II, Bst EII, Dra I, Eco RI, Eco RV, Hind III, Hpa I, Sal I, Sma I, Ssp I, Pst I, Xba I, and Xho I. They could be divided into three genomic clusters. Cluster 1 contained Ad 4p and Ad 4p 1-3; cluster 2 contained Ad 4a, ad 4a 1 and Ad 4b; whereas the chimpanzee Ad 4 genome type was the unique member of cluster 3. The degree of genetic variability within each cluster was minor. The genome types within one cluster display 95-99% pairwise comigrating restriction fragments (PCRF). However, the genetic space between the three clusters was large. The genome types between different clusters share only 25-46% PCRF. A comparative PCRF analysis performed with restriction endonucleases Apa I, Nar I, Nae I, Sac II, and Sma I recognizing exclusively G and C sequences and Dra I, Ssp I recognizing exclusively A and T containing sequences revealed that G and C rich regions were significantly more conserved than A and T rich regions.