Many factors have been implicated in autism onset, including excess or deficiency in toxic or essential metals and impaired antioxidant systems. Protection towards the damaging effects of reactive oxygen species (ROS) is afforded by antioxidant enzymes (superoxide dismutase, SOD, catalase, CAT, glutathione peroxidase, GPx), and non-enzymatic antioxidants such as metallothionein (MT). In blood samples from autistic children and healthy controls, three aspects were investigated: (i) the plasma concentration of 13 metals (Al, As, Ca, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Si, Zn) was measured by ICP-AES; (ii) the transcription of three MT isoforms (MT-1A, MT-1E and MT-2A) was assessed by real-time RT-PCR in peripheral blood leucocytes (PBMCs); (iii) the activity of SOD, CAT and GPx was assessed by spectrophotometric assays in red blood cells (RBCs). Autistic children showed significantly higher plasma levels of Zn, Ca, Fe, As, Ni, Cd and Si, higher mRNA expression of the MT isoforms in PBMCs, higher SOD activity and lower CAT activity in RBCs with respect to controls. These findings demonstrate a significant increase in both metal content and metallothionein expression together with an unbalance in the oxidative status in the blood of autistic children. (Contains 1 table and 4 figures.)