The core symptoms of autism spectrum disorder (ASD) include impaired social communication, repetitive behaviors, and restricted interests. No effective pharmacotherapy for these core deficits exists. Within the domain of social communication, the vasopressin system is implicated in social cognition and social signaling deficits of ASD, and represents a potential therapeutic target. We assessed the effects of a single 20 mg intravenous dose of the arginine vasopressin receptor 1A (V1a) antagonist, RG7713, on exploratory biomarkers (eye tracking), behavioral and clinical measures of social cognition and communication (affective speech recognition (ASR), reading the mind in the eyes, olfactory identification, scripted interaction), and safety and tolerability in a multicenter, randomized, double-blind, placebo-controlled, cross-over study of 19 high-functioning adult male subjects with DSM-IV Autistic Disorder (age 18-45 years; full scale IQ > 70; ABC-Irritability subscale â 1/213). Eye-tracking showed an increase in biological motion orienting preference with RG7713 (ES=0.8, p=0.047) and a non-significant improvement in the composite score (ES=0.2, p=0.29). RG7713 reduced ability to detect lust (ES=-0.8, p=0.03) and fear (ES=-0.7, p=0.07) in ASR. However, when all eight individual emotion subscales were combined into an overall ASR performance score, the reduction was non-significant (ES=-0.1, p=0.59). Thirteen adverse events were reported in 10 subjects; all were of mild (11/13) or moderate (2/13) severity. Although interpretation should be cautious due to multiple comparisons and small sample size, these results provide preliminary evidence from experimental and behavioral biomarkers, that blockade of the V1a receptor may improve social communication in adults with high-functioning ASD.