There is evidence of both immune dysregulation and autoimmune phenomena in children with autism spectrum disorders (ASD). We examined the hormone/cytokine leptin in 70 children diagnosed with autism (including 37 with regression) compared with 99 age-matched controls including 50 typically developing (TD) controls, 26 siblings without autism, and 23 children with developmental disabilities (DD). Children with autism had significantly higher plasma leptin levels compared with TD controls (p < .006). When further sub-classified into regression or early onset autism, children with early onset autism had significantly higher plasma leptin levels compared with children with regressive autism (p < .042), TD controls (p < .0015), and DD controls (p < .004). We demonstrated an increase in leptin levels in autism, a finding driven by the early onset group.