Objective: To assess the effectiveness of simple behavioral interventions at immunization on behavioral and biochemical indicators of distress in infants and parents in a primary care setting.Design: Subjects were enrolled sequentially to control (standard care) and intervention groups. Intervention parents (n = 57) were provided information about techniques to help their infants at immunization. Standard care parents (n=45) did not receive this information. Immunizations were videotaped and coded for infant and parent behaviors. Using a visual analog scale, parents rated their infant's and their own comfort at study enrollment, immediately after immunization, and at checkout. Saliva samples collected from infants and parents at study enrollment and at 15, 30, and 60 minutes after immunization were assayed for cortisol concentration by standard radioimmunoassay. Data were analyzed using 2 , analysis of variance, and general linear modeling. Patterns of salivary cortisol change after immunization were analyzed using hierarchical linear modeling.Setting: A single, urban pediatric practice during 2 summers (1997 and 1998). Results: Intervention parents were more likely to use a behavioral technique with their infants before immunization (PϽ.05). Total infant distress was shorter for intervention infants at immunization (PϽ.01), and these infants were rated as more comfortable by their parents (PϽ.001) immediately after immunization. Salivary cortisol levels were lower for intervention infants at 15, 30, and 60 minutes after immunization (PϽ.05). Conclusion:Simple behavioral interventions before immunization are associated with reductions in behavioral and biochemical indicators of infant distress.