Elevated whole blood serotonin (WB5-HT) is a well-replicated biomarker in autism spectrum disorder (ASD). Decreased platelet serotonin receptor 5-HT[subscript 2A] binding has been reported in ASD. WB5-HT levels and platelet 5-HT[subscript 2A] specific binding were obtained from 110 individuals with ASD and 18 controls. Individuals with ASD had significantly higher WB5-HT levels than controls. There was no difference in the platelet 5-HT[subscript 2A] specific binding between groups. Multiple regression analyses revealed that platelet 5-HT2A binding significantly predicted WB5-HT in the control sample but not in the ASD sample. These results indicate that the relationship between WB5-HT and platelet 5-HT[subscript 2A] binding differs depending on ASD diagnosis, suggesting differences in platelet 5-HT system regulation in ASD.