Possible explanations for the well-replicated platelet hyperserotonemia of autism include an alteration in the platelet's handling of serotonin (5-hydroxyserotonin, 5-HT) or an increased exposure of the platelet to 5-HT. Measurement of platelet-poor plasma (PPP) levels of 5-HT appears to provide the best available index of in vivo exposure of the platelet to 5-HT. Mean (± SD) concentrations of PPP 5-HT observed in the autism (N = 18), hyperserotonemic subgroup (N = 5) and control (N = 24) groups were 0.86 ± 0.53, 0.87 ± 0.43 and 0.86 ± 0.36 nM, respectively. The results suggest that the hyperserotonemia of autism is not due to increased exposure of the platelet to 5-HT and make it more likely that the factor(s) contributing to the hyperserotonemia of autism have to do with the platelet's handling of 5-HT.