The Mixtec languages are members of the Mixtecan branch of the Otomanguean language family, one of the largest and most important linguistic groups of Mesoamerica. Mixtec is presently spoken by 250,000 persons living in the Mexican states of Oaxaca, Puebla and Geuerrero. A combination of the methodologies of modern dialectology and historical-comparative linguistics is applied to a large body of published and unpublished material from the Mixtec languages and dialects. A structural framework for interpreting the data is provided by the analysis and comparison of 16 modern Mixtec phonological systems. This comparison also provides support for hypotheses about the Proto-Mixtec phonological system. An overview of the reconstructed units and other phonological characteristics of Proto-Mixtec is followed by a detailed presentation of the vowel correspondences for the six Proto-Mixtec vowels and their developments into the modern varieties. Data presented in support of this reconstruction include 188 cognate sets drawn from 122 varieties of Mixtec. From the patterns of regional development revealed by this analysis and reconstruction, inferences are drawn concerning prehistoric population movements and spheres of cultural influence within the Mixtec speaking area. Stages of diversification are proposed, corresponding to the periods of action of major phonological processes. Although subgrouping by genealogical classification is not attempted, a grouping into dialect areas is achieved by a combination of diagnostic linguistic features, both phonological and lexical. These areal groupings are suggested as candidates for the reconstruction of intermediate stages between Proto-Mixtec and the modern varieties