Background: Significant resources are used for acute illnesses in children. Identifying predictors of resource use can focus interventions to reduce this use. Objective: To determine the relative effects of maternal, infant, social milieu, and demographic characteristics, the mother-child interaction, and perception of illness severity on the use of resources during acute illnesses in children. Design: At the 2-week and 6-, 15-, and 24-month well-child care visits of a cohort of mother-infant dyads, the mother-well-child interaction was assessed by using the Biringen Emotional Availability Scales, and data were gathered regarding maternal depression and sense of competence, infant temperament, maternal social support, the home environment, and demographic characteristics. At each of the cohort's 1983 ill-child care visits during 30 months of follow-up, the mother-ill-child interaction was assessed by using the Emotional Availability Scales, and mothers and pediatricians independently assessed illness severity using the Acute Illness Observation Scales. Resources used during the illnesses-over-the-counter and prescription medications, tests, hospitalizations, follow-up visits, and the emergency department-were assessed. Setting: A hospital primary care center and an urban and a suburban private practice. Patients: Between February 1, 1995, and March 30, 1998, a consecutive sample of 380 dyads were asked to enroll at the 2-week well-child care visit; 316 (83.2%) consented, and complete data were available for analysis of 243 dyads. Main Outcome Measures: A path analytic framework using a structural equation model assessed the presence and strength of predictive relationships between demographic, maternal, infant, and social milieu data, the Biringen Emotional Availability Scales, and the Acute Illness Observation Scales and the main outcome measure, resource use. Results: Three variables predicted greater mean resource use during each acute illness episode: a less optimal mother-child interaction (β = -.53), lower scores for parenting sense of competence (β = -.26), and greater perception of illness severity by mothers (β =.33). By using the coefficient of determination (R 2), these 3 predictors account for 55% of the reliable variance in resource use during acute illnesses. Conclusion: The quality of the mother-child interaction, maternal sense of competence, and maternal assessment of severity of the illness are major predictors of resource use during acute pediatric illnesses, and should be important foci of interventions to reduce resource use.