Cytokines are the main mediators of inflammation in rheumatoid arthritis (RA). Thus, Th2 cytokines--such as IL-4 and IL-10--have protective properties to this disease. In opposite, the Th1 cytokines--such as IL-2 and IFN-gamma--are supporting proinflammatory microenvironment in joints from patients with RA. The imbalance of Th1/Th2 cytokine steady state may play an important role in the pathogenesis of rheumatoid arthritis. The evaluation of this imbalance leads up to the possibility of pathohistological discrimination in this disease. In this context, we investigated Th1- (IFN-gamma, IL-2) and Th2 (IL-10, IL-4)-cell-derived cytokine mRNA expression in two novel pathohistological main-types of RA synovial membrane (SM). These main-types are characterized by different tissue-infiltrating inflammatory cells and different extent of SM destruction. Our findings showed that expression of IL-10 mRNA was an outcome of histological main-type I (p<0.001), whereas expression of IFN-gamma and IL-2 were mainly associated with pathohistological main-type II (p<0.005, p<0.05). Surprisingly, IL4 was not differential expressed and could be associated with another special T cell subset in this disease. These results suggest that Th1/Th2 balance is biased to Th2 cytokines within main-type I and Th1 cytokines in main-type II.