Genetic drift and natural selection were analyzed in a genetically isolated Zapotec-speaking community in the Valley of Oaxaca, southern Mexico. Moderately intense genetic drift and selection potentials were found. Potential for drift was related to (1) the small effective size of the population, and (2) the exceptionally low number of migrants into the population. Potential for selection was due to (1) an unusually high variance in fertility, and (2) a high contribution of prereproductive mortality. Significant potential for genetic evolution was found due to genetic drift and natural selection.