There is growing evidence of an association between physical illness and problem behavior in children with developmental disabilities. Such behavior can compromise school performance. Therefore, the purpose of the present study was to evaluate, using a group design, the effectiveness of medical intervention alone (N = 11) versus behavioral plus medical intervention (N = 10) for illness-related problem behavior in a school setting. Following intervention, the behavioral plus medical intervention group showed lower levels of problem behavior and completed more academic tasks than did the medical intervention alone group. The results are discussed with respect to the concept of illness and pain as a setting event for problem behavior. The need for research to develop algorithms that allow one to select the best combination of medical and behavioral interventions for specific illnesses and contexts is noted. (Contains 2 figures and 1 table.)