Strains of Mycoplasma hominis isolated from different tissues of patients with a variety of disease processes and from cell culture substrates show marked phenotypic and genotypic heterogeneity, as determined by their antigenic and isozyme properties and by [3H]DNA-DNA hybridization and DNA cleavage pattern analyses. Strains isolated from the same tissues (blood of postpartum patients or human urogenital tract or cell culture substrates) have very high genomic homology and form clusters of similar strains. Clusters of strains that colonize similar specialized urogenital tissues may initiate diseases that reflect damage to the particular tissue colonized. Antigenic markers such as those for attachment components for different strain clusters may help determine the role, if any, played by strain differences in the etiology of a family of urogenital diseases.