The hormone melatonin has an important influence on the sleep-wake cycle and daily rhythms, is involved in fetal development and neurodevelopment, is used in the treatment of sleep problems, and has a role in gut function. Thus, there is a strong theoretical basis for studying melatonin in autism. A compelling reason for investigating melatonin in autism also comes from several previous studies that have found lower melatonin levels or decreased urinary excretion of the main melatonin metabolite in individuals with autism. Melatonin production has not been examined in children with autism younger than 5 years old. Examination and characterization of melatonin production in toddlers with autism may lead to measures useful for early screening for autism risk, for predicting behavioral phenotype, and for guiding intervention. The immediate objective of the proposed research is to compare the production of melatonin by young children with autism to typically developing children. Specifically, we will see if the nighttime excretion rate of melatonin sulfate is markedly lower in the children with autism, whether there is a subgroup of children with autism having very low excretion; whether low nighttime excretion of melatonin sulfate is associated with sleep problems; and whether low daytime melatonin sulfate excretion is associated with gastrointestinal problems. We also will determine whether other hormones with day-night variation are similar in children with autism and in typically developing children. Establishing the presence and characterizing the extent and nature of altered melatonin production in young children with autism has several important implications: (1) the measure may prove useful in early screening for autism risk; (2) may provide an indication of which areas of behavior or functioning might be most affected (e.g., sleep problems, GI disturbances); (3) may serve to guide early intervention strategies; (4) may function as a useful predictor and surrogate marker of response to intervention; and (5) may provide leads to related neurobiological alterations and mechanisms, and may suggest specific candidate genes of interest in autism. Larger second phase studies are planned to establish more fully the initial findings, to replicate the expected behavioral associations, and to examine the genetic and biochemical basis of the altered secretion/excretion. National Institutes of Health funding will be sought for the follow-up studies that may well take a multi-center approach. The urine samples collected should also permit or facilitate future investigations examining day-night variation in other systems, levels of sex hormones, markers of oxidative stress, and environmental exposures in toddlers with autism. The research has the potential to help families and children affected by autism by improving early detection/screening, by improving treatment, and by increasing basic understanding of the origins of autism. By moving the research on melatonin in autism to younger children, the research has the potential to greatly improve the clinical utility of the measure. Characterizing the relationship of the alteration in melatonin to disturbances in sleep behavior and gastrointestinal functioning may lead to an improved understanding of the bases for these problems in autism.