Background and Objectives: Over-production of the type II T-helper cells (Th2-shfit) has been suggested as a candidate mechanism for the etiology in at least one subgroup of schizophrenia. Hitherto, empirical evidence is derived mostly from in vitro cytokine production. Due to frequently undetectable serum levels of the major Th2 cytokine Interleukin-4 (IL-4), direct evidence, measured as a ratio between Th1/Th2 (type I/type II T-helper cells) characteristic cytokines, is rare. This study aimed at examining whether a serum Th2-shift occurs in schizophrenia. Th2-shift was defined as markedly decreased serum IFN-gamma/IL-4 and/or IFN-gamma/IL-10 and/or IL-2/IL-4 ratios, compared with healthy subjects. Methods: Totally 74 subjects were recruited: 37 drug-free subjects with schizophrenia according to ICD-10 and DSM-IV as well as 37 age- and sex-matched healthy controls. Cytometric Bead Array, which enables a simultaneous measurement of 6 cytokines with the same volume of test sample, was used to assess serum Th1/Th2 ratios and cytokine levels. Non-parametric Mann-Whitney U test was utilized to detect the diversities in serum Th1/Th2 ratios and cytokine levels between both diagnostic groups. Results: Subjects with schizophrenia showed significantly reduced serum IFN-gamma/IL-4 and IFN-gamma/IL-10 ratios if compared to healthy controls. If both sexes analyzed separately, males with schizophrenia had significantly reduced serum IFN-gamma/IL-10 ratios, while female patients showed markedly decreased serum IFN-gamma/IL-4 ratios. Conclusions: A clear Th2-shift was observed in schizophrenia. Males and females with schizophrenia seemed to have different profiles of Th2-shift. Th1/Th2 ratios appeared to play different roles in the pathology of males and females with schizophrenia.