OBJECTIVE: This study examines the efficacy of intravenous porcine secretin for the treatment of autism. METHODS: Using a randomized, double-blind, placebo-controlled crossover design, 20 subjects with autistic disorder received either a secretin or placebo infusion at baseline and the other substance at week 4. Subjects were given the Autism Diagnostic Interview-Revised, the Autism Diagnostic Observation Schedule-Generic (ADOS-G), and other pertinent developmental measures at baseline and at weeks 4 and 8 to assess drug effects. RESULTS: For the primary efficacy analysis, change of ADOS-G social-communication total score from week 0 to week 4, no statistically significant difference was obtained between placebo (-1.0 +/- 2.4) and secretin groups (-0.7 +/- 1.4; t 0.34, df 18, P less than.74). No significant differences were obtained for the other measures, including when all 20 subjects were compared by paired t-test from baseline to 4 weeks after secretin infusion. CONCLUSION: There was no evidence for efficacy of secretin in this preliminary randomized controlled trial. These data were collected as part of a multicenter study with the University of California-Irvine and the University of Utah.