This study examined the relative importance of and developmental changes in biologically-based child variables (infant vagal tone and infant difficultness) and parental contextual variables (maternal behavior during pain and maternal sensitivity) in the prediction of infant pain behavior during immunization. Sixty infant-mother dyads were assessed when infants were approximately 6 or 18-months of age. During the first session, mothers completed a measure of infant difficultness, infants' resting EKG signals were recorded, and maternal sensitivity was rated. During the second session, infants' immunizations were video-recorded and maternal vocalizations and infant pain behavior were rated. At 6-months of age, 44% of the variability in infant pain behavior was predicted by infant difficultness and mothers' vocalizations during immunization. At 18-months of age, 35% of the variability in infant pain behavior was predicted by maternal sensitivity and infant vagal tone level. Children's emotion regulation skills and socialization histories may underlie age-related changes in the predictors of their pain.