There is growing interest in the role that physical illness and pain might play in exacerbating problem behavior in individuals with developmental disabilities. Assessment of these factors, however, is often difficult since many individuals have minimal verbal communication skills. In response to this difficulty, we developed a sequential method of assessment involving retrospective and prospective measurement strategies. We found that the frequency and intensity of problem behavior was greater on “sick” days than on “well” days. Further, the higher the level of pain, the greater was the frequency and intensity of problem behavior. We discuss the concept of pain as a setting event for problem behavior and the intervention strategies that follow from this conceptualization.