To understand the molecular basis of parasite-specific anergy in human lymphatic filariasis caused by the nematode Wuchereria bancrofti, parasite antigen-dependent cellular proliferation and cytokine gene expression were investigated. By reverse transcriptase polymerase chain reaction (RT-PCR), the levels of cytokine mRNA were determined in the peripheral blood mononuclear cells (PBMCs) of different clinical groups of filariasis patients. This includes individuals with circulating microfilariae (MF), patients with chronic lymphatic obstruction (CP), and exposed but uninfected individuals (EN). Those with CP exhibited both a Th2 and a Th1 parasite antigen-driven response. In PBMCs from those with MF, there was a marked downregulation of cellular response to parasite antigens, with lowered expression of Th1-specific cytokines (IFN-γ and IL-2) and this was paralleled by increased IL-10 expression. The EN individuals had a purely Th1-type pattern with absence of IL-4 and IL-5 expression. Further, the mRNA expression of the costimulatory surface marker, CD80 (B7-1), was not associated with either disease status or IL-10 expression. There was a significant negative correlation between IL-10 mRNA expression and PBMC proliferation in the MF individuals, thus indicating the possible role of IL-10 in antigen-specific hyporesponsiveness.