Objectives: A recent patient series reported the incidental findings of improved social and language skills in 3 children with autistic spectrum disorders after the administration of secretin, a peptide hormone. However, a subsequent study did not find evidence for a drug effect. Parents are seeking treatment with secretin despite the absence of empirical investigations demonstrating amelioration in autism symptomology. In order to more precisely measure the effects of secretin, this study investigated the effect of a single intravenous dose of porcine secretin on 12 autistic children through a randomized, double-blind, placebo-controlled, crossover study. Children were assessed on objective language and on social, neuropsychological, and gastrointestinal measures to evaluate drug effects. The study was conducted over a 16-week trial. The results indicated that significant differences were not observed on the majority of the dependent variables. Statistically significant differences were observed on measures of positive affect and activity level following secretin infusion. In general, the autistic children did not demonstrate the improvements described in the initial retrospective report.