OBJECTIVE Clinical case reports have suggested that the behaviors of children with autism spectrum disorders may improve with fever. The purpose of this study was to investigate the effect of illness on behaviors of children with autism spectrum disorders. Understanding the role of fever, if any, may be informative regarding causative mechanisms of and treatment opportunities for autism. METHODS We conducted a prospective study of 30 children (aged 2-18 years) with autism spectrum disorders during and after an episode of fever. Parent responses to the Aberrant Behavior Checklist were collected during fever (body temperature > or = 38.0 degrees C/100.4 degrees F), when fever had abated and the child was asymptomatic, and when the child had been fever-free for 7 days. Data were compared with those collected from parents of 30 age-, gender-, and language skills-matched afebrile children with autism spectrum disorders during similar time intervals. RESULTS Fewer aberrant behaviors were recorded for febrile patients on the Aberrant Behavior Checklist subscales of irritability, hyperactivity, stereotypy, and inappropriate speech compared with control subjects. Per expectation, lethargy scores were greater during fevers, and all improvements were transient. Data from patients with fever were stratified on variables related to illness severity. In the majority of these subgroup comparisons, the data suggested that effects from fever persisted in the less sick patients as well as in those with more severe illness. CONCLUSIONS We documented behavior change among children with autism spectrum disorders during fever. The data suggest that these changes might not be solely the byproduct of general effects of sickness on behavior; however, more research is needed to prove conclusively fever-specific effects and elucidate their underlying biological mechanisms (possibly involving immunologic and neurobiological pathways, intracellular signaling, and synaptic plasticity).