The effects of incentive on sustained attention and autonomic regulation among boys exposed in utero to opiates were studied. Respiratory sinus arrhythmia (RSA), an indicator of autonomic regulation, was quantified during sustained attention in 3 groups of 7- to 12-year-old boys. RSA is a component of heart rate variability controlled by cortical influences and affected by changes in demand for attention. The Gordon Diagnostic System-Distractibility Task was performed with and without monetary reward. A cartoon task and a video game were used as measures of interest. Although opiate-exposed boys did not differ in performance as a function of incentive or interest, they had a tendency to perform more poorly overall across tasks. Alcohol exposure rather than opiate exposure covaried with autonomic regulation, with greater RSA decreases being associated with more alcohol exposure. Post hoc analyses revealed that the alcohol- and opiate-exposed boys responded with these hyperreactive RSA changes along with poorer performance.