Ten studies designed to evaluate the psychological and behavioral effects of the antiasthma agent theophylline in children have been carried out to date. In this review, we evaluate the strengths and weaknesses of those investigations and discuss whether theophylline is responsible for learning disabilities or behavioral disorders such as hyperactivity. We also discuss the similarities between studies of theophylline and those of other xanthines, such as caffeine, to suggest that some persons appear to have a heightened response to these substances and would benefit from closer monitoring, not only of serum drug levels but also of their consumption of food and beverages that contain caffeine. In addition, we describe strategies for examining whether a functional relationship exists between theophylline use and behavioral and psychological changes in children.