Abstract Autoimmunity may have a role in autism, although the origins of autoimmunity in autism are unknown. CD4 +CD25high regulatory T cells play an important role in the establishment of immunological self-tolerance, thereby preventing autoimmunity. The authors are the first to study the frequency of CD4+CD25 high regulatory T cells in the blood of 30 autistic and 30 age- and sex-matched healthy children. Patients with autism had significantly lower frequency of CD4+CD25high regulatory T cells than healthy children (P < .001). These cells were deficient in 73.3% of children with autism. Autistic patients with allergic manifestations (40%) and those with a family history of autoimmunity (53.3%) had a significantly lower frequency of CD4+CD25high regulatory T cells than those without (P < .01 and P < .001, respectively). In conclusion, CD4+CD25 high regulatory T cells are deficient in many children with autism. Deficiency of these cells may contribute to autoimmunity in a subgroup of children with autism. Consequently, CD4+CD25high regulatory T cells could be new potential therapeutic targets in these patients.