The interactive behaviors of 17 American Indian mothers and their premature infants and selected maternal and infant factors affecting those behaviors were measured using naturalistic observation and the Home Observation for Measurement of the Environment (HOME) Inventory at 3, 6, and 12 months corrected infant age. The frequency of some maternal behaviors changed over the first 12 months. Mothers spent less time holding, looking at, touching, and interacting with their premature infants and more time uninvolved as the infant aged. Maternal education and infant illness severity were associated with mother-infant interactive behaviors and HOME Inventory scores. These findings emphasize the importance of maternal and infant factors affecting the interactions between American Indian premature infants and their mothers.