Serotonin and its precursor tryptophan have long been implicated in the pathophysiology of autistic disorder (autism). Recent genetic evidence implicates involvement of a gene encoding tryptophan 2,3-dioxygenase, a rate-limiting enzyme in tryptophan's major metabolic pathway, the kynurenine pathway, in autism. To test activity of the kynurenine pathway in autism, plasma kynurenine levels were measured in 30 drug-free autistic children (mean age (SD)=6 years 0 months (2 years 9 months)) and 29 age-, race- and gender-matched healthy comparison subjects (mean age (SD)=6 years 5 months (2 years 6 months)) using high-performance liquid chromatography. No difference was found in plasma kynurenine levels between the study groups. In the autistic children, plasma kynurenine levels did not correlate with autistic behaviors or IQ. These results do not support a role for abnormal global function of the kynurenine pathway; however, the status of this pathway in the brain remains unknown.