A prospective study was undertaken in Ladakh, India, a high-altitude region of the Himalaya, to investigate the effects of small average birth size on neonatal mortality. While such studies exist from high-altitude regions of the New World and shed light on the adaptive status of high-altitude-dwelling populations there, this is the first to examine this relationship in the Himalaya. In a sample of 168 newborns, birthweight and other anthropometric measurements were reduced relative to Andean and Tibetan newborns. Logistic regression and hazard analysis showed that neonatal biological characteristics such as weight, fatness, and circumferences were important predictors of survival probabilities of infants, especially in the neonatal period. Low Rohrer's Ponderal Index (PI) was particularly strongly related to poor survival outcome. Males and females showed no significant differences in mortality risk. Data derived from reproductive histories revealed that neonatal mortality accounted for 70–80% of total infant mortality in Ladakh. Compared to other high-altitude studies, small newborn size in Ladakh was associated with much higher mortality risks; mortality risk rose dramatically with birthweights below the mean (2,764 grams), which characterized 50% of all newborns. It is argued that newborns in Ladakh are subject to strong directional selective forces that favor higher birthweights that incur lower risks of neonatal mortality, while Andean infants are subject to relatively mild selection pressure at both ends of the birthweight distribution. Given the overall small size at birth of Ladakhi newborns and the poor survival outcomes of newborns below the mean, it is suggested that this population is less well adapted in a biological sense to the stresses inherent in this high-altitude environment than are Andean populations, perhaps due to the relatively recent colonization of the area and the substantial genetic admixture that has occurred in the past. © 1994 Wiley-Liss, Inc.