Covering about 723,000 hectares, Calakmul Biosphere Reserve comprises the largest tract of protected tropical forest in Mexico. Despite its geographic isolation, the reserve and its immediate surroundings experienced considerable population growth during the 1980s and 1990s, placing increasing pressure on resources in the region in general and on the biosphere reserve in particular. The following study examines data from 1980, 1990, and 2000 censuses of population and housing in Mexico to document geographic patterns of demographic change in the region, to identify the main causes of recent population change over time, and to explore relationships between human population and land use patterns in this part of Mexico at the end of the 20th century. Results of the study indicate that rapid population growth continued in the region through the 1990s, affecting most localities in or near Calakmul, in large part due to continued migration (likely) from other parts of Mexico. Census data reveal the presence of economic activities in or near Calakmul incompatible with conservation, and satellite imagery indicates agriculture in several parts of the biosphere, including the nuclear zone. Statistical analysis of the former indicates a significant relationship between population and agriculture, while an evaluation of agricultural suitability in and around Calakmul indicates mixed though often limited potential. As a result, continued population growth in this area will expand the agricultural footprint, likely straining Calakmul management to maintain the conservation function of the biosphere reserve.