The thymus plays an important role in the development of the immune system, yet little is known about the patterns and sources of variation in postnatal thymic development. The aim of this study is to contribute cross-cultural data on thymus size in infants from two South American native populations, the Tsimane of Bolivia and the Pumé of Venezuela. Thymic ultrasonography was performed and standard anthropometric measures collected from 86 Tsimane and Pumé infants. Patterns of infant growth and thymus size were compared between the two populations and the relationship between nutritional status and thymus size was assessed. Despite nearly identical anthropometric trajectories, Tsimane infants had larger thymuses than Pumé infants at all ages. Population, infant age, and infant mid-upper arm circumference were significant predictors of thymus area in the Tsimane and Pumé infants. This finding reveals a cross-cultural difference in thymus size that is not driven by nutritional status. We suggest that future studies focus on isolating prenatal and postnatal environmental factors underlying cross-cultural variation in thymic development. Am. J. Hum. Biol., 2012. © 2012 Wiley Periodicals, Inc.