This is the first report of antipredator nest defense by iguanian lizards. Female Texas Horned Lizards (Phrynosoma cornutum) and Round-tailed Horned Lizards (P. modestum) consistently exhibited vigorous nest-site defensive behaviors (butting, open-mouth attacks, and biting attacks) when experimentally approached in the field by a potential predator of reptilian eggs, Western Patch-nosed Snakes (Salvadora hexalepis). During both prenesting and postnesting snake trials, such defensive attack behaviors by the female lizards were absent. Females of a viviparous congener, Greater Short-horned Lizards (Phrynosoma hernandesi), failed to exhibit postpartum defensive behaviors to S. hexalepis, and newborns did not associate in proximity to their mothers. Nest-site defense is suggested to be the ancestral behavior in the genus Phrynosoma, and it might have been lost during the evolution of viviparity in certain species. Previous failures to detect nest defense behavior in Phrynosoma, and in related clades of iguanian lizards, might be attributable to the absence of observations at nest sites after egg laying by such lizards, especially because these behaviors occur only during brief time windows of potential nest detection by egg-hunting snakes. Similar trials with other iguanian lizards and potential nest predators could reveal further examples of parental care in this diverse lineage of lizards.