Serovars E, F, and D are the most prevalent Chlamydia trachomatis strains worldwide. This prevalence may relate to epitopes that enhance infectivity and transmission. There are numerous major outer membrane protein (MOMP) gene ( omp1 ) variants described for D and F but few for E. However, omp1 constant regions are rarely sequenced, yet, they may contain mutations that affect the structure/function relationship of the protein. Further, differentiating variants that occur as a result of selection from variants that contain random mutations without biologic impact is difficult. We investigated 67 urogenital E serovars and found 11 (16%) variants which contained 16 (53%) nonconservative amino acid changes. Using signature-pattern analysis, 57 amino acids throughout MOMP differentiated the E sequence set from the non-E sequence set, thus defining E strains. Four E variants did not match this signature-pattern, and, by phenetic analyses, formed new phylogenetic branches, suggesting that they may be biologically distinct variants. Our analyses offer for the first time a unique approach for identifying variants that may occur from selection and may affect infectivity and transmission. Understanding the mutation trends, phylogeny, and molecular epidemiology of E variants is essential for designing public health control interventions and a vaccine. ( J. Clin. Invest. 1997. 99:475-483.)