OBJECTIVE: To compare the interactive behaviors of American Indian mothers and their premature infants with those of African American mothers and their premature infants. DESIGN: Descriptive, comparative study. SETTING: Three neonatal intensive care units and two pediatric clinics in the southeast. PARTICIPANTS: Seventy-seven mother/infant dyads: 17 American Indian mother/infant dyads and 60 African American mother/infant dyads. METHODS: Videotapes of mother/infant interactions and the Home Observation for Measurement of the Environment (HOME) were used to assess the interactions of the mothers and their premature infants at 6 months corrected age. RESULTS: American Indian mothers looked more, gestured more, and were more often the primary caregivers to their infants than the African American mothers. American Indian infants expressed more positive affect and gestured more to their mothers, whereas African American infants engaged in more non-negative vocalization toward their mothers. African American mothers scored higher on the HOME subscales of provision of appropriate play materials and parental involvement with the infant. American Indian mothers scored higher on the opportunities for variety in daily living subscale. CONCLUSION: Although many of the interactive behaviors of American Indian and African American mother/infant dyads were similar, some differences did occur. Clinicians need to be aware of the cultural differences in mother/infant interactions. To optimize child developmental outcomes, nurses need to support mothers in their continuation or adoption of positive interactive behaviors.