In the absence of certain consistent biomarkers, the diagnosis of autism is based on well-defined core behavioral symptoms: abnormal social interactions and social communication and repetitive and/or limited interests. Many medications, including fluoxetine and risperidone, have been used to treat symptoms associated with autism. Risperidone, an atypical antipsychotic that blocks D2 and 5HT2A receptors, has been approved by the U.S. Food and Drug Administration (FDA) to reduce repetitive behavior and self-injurious behavior in children with autism. Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), is being evaluated by the FDA for anxiety and repetitive behaviors in autistic individuals. Serotonin dysregulation is one theory for the etiology of autism (reviewed by Pardo and Eberhart, 2007) and has been linked to comorbid behaviors associated with autism such as depression, anxiety, mood, impulsivity, and aggression (reviewed by Soorya et al ., 2008; West et al., 2009). Both risperidone and fluoxetine act in the serotonin system. Risperidone antagonizes the serotonin 2A receptor and fluoxetine blocks the serotonin transporter by increasing the amount of serotonin available in the synapse. Animal models are a useful tool in the search for a pharmacological treatment for the core symptoms of autism. One approach is to select inbred strains of mice that demonstrate behavioral characteristics that have face validity for autism. The social approach test was developed to identify deficits in social interaction in which a mouse subject can choose between a social and nonsocial environment (Moy et al. 2004; Nadler et al. 2004; Moy et al. 2007; Yang et al. 2007; Farlane et al. 2008; Journal for Specialists in Pediatric Nursing 14(3) (2009), pp. 183-191 doi:10.1111/j.1744-6155.2009.00196.xM Yang, ML Scattoni, V. Zhodzishsky, T. Chen, H Caldwell, WS Young, HG McFarlane, JN Crawley, Social approach behaviors are similar across cycles of conventional versus reverse illumination, and in replicates across cohorts, in mutant mice BTBR T+ tf/J, C57BL/6J and vasopressin 1B receptor, Frontiers in. Behavioral Neuroscience 1 (2007. doi:10.3389/neuro.08.001.2007M Yang, V. Zhodzishsky and JN Crawley, Social Deficits). in BTBR T+tf/J Mice are Unchanged by Cross-Fostering with C57BL/. 6J Mothers, International Journal of Developmental Neuroscience 25(8) (2007), pp. 515–521. doi:10.1016/j.ijdevneu.2007.09.008