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Our object in this paper is to analyze the opportunity for natural selection and gene flow in an isolated Zapotec-speaking community in the valley of Oaxaca, southern Mexico, that is undergoing a secular increase in body size. Surveys were conducted in the community in 1968, 1978, and 2000, including anthropometric and census data. No secular change was found in the growth status of schoolchildren and adult height between 1968 and 1978; subsequently, major secular gains in height occurred among children and adolescents between 1978 and 2000. The 1978 household data were used to compute gene flow (3.3%) and opportunity for selection intensity (I 1.312). Migration and other demographic information was obtained from household census data for 1978 and 2000, and mortality information was extracted from community records and archives. These data were used to compute gene flow and opportunity for natural selection. Gene flow increased from 3.3% to 4.7% and intensity of natural selection decreased from 1.312 to 0.272 from 1978 to 2000. Variance in fertility increased slightly over time (12.25 to 13.69). Opportunity for selection was dominant during the prereproductive period in 1978, but approached 0 for the mortality component in 2000, resulting in a marked decrease in the mortality component (Im) of selection (0.626 and 0.019, respectively) and total opportunity for selection (I 1.312 and 0.272, respectively). Secular increase in height and markedly decreased opportunity for natural selection (I) were associated with better health and nutritional conditions. Genotype-environment interaction and environmental influences are apparently the predominant causes of the secular trend. If natural selection plays a role in causing the secular trend, it is a small one.