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 (plus or minus SD) concentrations of PPP 5-HT observed in the autism (N = 18), hyperserotonemic subgroup (N = 5) and control (N = 24) groups were 0.86 plus or minus 0.53, 0.87 plus or minus 0.43 and 0.86 plus or minus 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.