In 1998, Horvath et al. (1998) observed a marked improvement in speech, eye contact, and attention in autistic children five weeks after treatment with secretin, which ocurred in the course of an endoscopic investigation. Since autism is hypothesized to be a hypoglutamatergic disorder we investigated the in vivo effects of secretin on extracellular amino acids in the rat brain. Studies were carried out on freely moving rats with microdialysis probes in the hippocampus. Amino acids were examined using tandem mass spectroscopy and HPLC/fluorometric detection. Following secretin injection (8.7 microg/kg i.p.), considerable increases in microdialysate glutamate and gamma-aminobutyric acid (GABA) levels were observed; other amino acids were not affected. The observed increased microdialysate concentrations of glutamate and GABA following secretin application may explain the results of the Horvath study.