BACKGROUND/AIMS: The prevalence of autism spectrum disorders (ASDs) is 1 in 300 children in the US. ASDs are characterized by impairments in social relatedness and communication, repetitive behaviors, abnormal movement patterns, and sensory dysfunction. Pre-pubertal age children with ASDs were assessed for metabolites in the methionine cycle-transsulfuration and androgen pathways, and for present physical development/behaviors indicative of hyperandrogenicity. METHODS: The Institutional Review Board of the Institute for Chronic Illnesses (Office for Human Research Protections, US Department of Health and Human Services IRB number: IRB00005375) approved the present study. Sixteen consecutive pre-pubertal age children (</=11 years old; mean +/- SD: 5.9 +/- 2.1 years old) with previously diagnosed ASDs that presented to the Genetic Centers of America for outpatient care were evaluated. RESULTS: Significantly (p < 0.01) increased levels of serum/plasma dehydroepiandrosterone and serum total testosterone relative to the age- and sex-specific normal laboratory reference ranges were observed. Conversely, serum follicle-stimulating hormone levels were significantly (p < 0.01) decreased. Plasma-reduced glutathione (p < 0.01), plasma cysteine (p < 0.01), plasma methionine (p < 0.01), serum cystathionine (p < 0.05), and serum homocysteine (p < 0.01) were all significantly decreased. CONCLUSION: The results suggest a possible cyclical interaction between the methionine cycle-transsulfuration and androgen pathways in some children with ASDs. Copyright (c) 2006 S. Karger AG, Basel.