The capsid protein sequences of 10 representative parvoviruses were aligned against the sequence and three-dimensional structure of canine parvovirus (CPV). The structure of CPV was then analyzed after mapping onto it position-dependent sequence similarity scores and the locations of residues that are phenotypically important in other parvoviruses. Antigenicity is primarily associated with external exposed loops of high sequence variability. Amino acids in the canyon, a surface depression encircling each fivefold axis, are well conserved, but may have a function other than external receptor binding. Residues important to parvoviral cell specificity and erythrocyte binding are scattered near the rim of a less-conserved depression near the twofold axis, and on a shoulder of the threefold spike. The number of residues involved in various interactions and their conservation and properties suggest that uncoating may involve separation of fivefold and twofold related subunits before those related by threefold symmetry. The inner surface residues of the capsid are generally more highly conserved than those on the outer surface, presumably due to interactions with DNA, although the binding site that contains ordered DNA in the structure is not especially conserved.