Autism is characterized by social deficits, communication and language impairments, narrow restricted interests, repetitive behaviors, inattention, and hyperactivity. While selective serotonin reuptake inhibitors have demonstrated efficacy in treating core symptoms of autism, norepinephrine reuptake inhibitors have demonstrated efficacy in symptoms of attention-deficit hyperactivity disorder (ADHD). An open, retrospective clinical study with venlafaxine evaluated its effect on core symptoms of autism as well as associated features of ADHD. Ten consecutive subjects meeting Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), criteria for an autism spectrum disorder were treated with venlafaxine, initiated at 12.5 mg per day and adjusted on a flexible basis. Six of 10 completers were judged to be sustained treatment responders, by scoring 1 (very much improved) or 2 (much improved) on the Clinical Global Impressions improvement scale. Venlafaxine was effective in low dosages (mean, 24.37 mg/day; range, 6.25 to 50 mg/day) and was well tolerated. Improvement was noted in repetitive behaviors and restricted interests, social deficits, communication and language function, inattention, and hyperactivity. Controlled treatment trials with venlafaxine are warranted in autism spectrum disorders.