Objective : The study investigated whether baseline plasma oxytocin (OXT) concentrations might moderate the effects of nasally administered OXT on social orienting. ; Methods : Thirty-one males with Autism spectrum disorder (ASD) and thirty healthy males participated in a double-blind placebo-controlled crossover trial. After administration of the compound, participants were viewing pictures from the International Affective Picture System that represented a systematic variation of pleasant, unpleasant and neutral scenes with and without humans. The outcome measures were a cardiac evoked response (ECR) and a cortical evoked long latency parietal positivity (LPP). ; Results : Males with ASD had significantly higher plasma baseline levels than the controls. In the absence of general treatment effects, higher baseline concentrations were found to be associated with larger treatment effects, particularly in the group of males with ASD. Higher post-treatment plasma OXT concentrations were found to be associated with smaller treatment effects and larger orienting responses in the placebo situation in the group of controls. ; Conclusions : We interpret our findings as suggesting that it is the central availability of OXT determining how much of the nasally administered OXT will become centrally absorbed and how much of it will become released into the bloodstream.