It has been seen that advanced stage oral squamous cell carcinoma is associated with impaired T-cell function and higher antibody response. In order to find out if such immune disregulation is associated with alteration of T-helper (Th) type CD4+ T-cell phenotype leading to altered cytokine production, we studied the Th-like cytokine profile in 35 oral squamous cell carcinoma patients and 21 normal controls. Concomitant expression of both Th1 and Th2 cytokine genes was studied by reverse transcription and Polymerase Chain Reaction (PCR) based amplification (RT-PCR) of mRNA extracted from freshly isolated peripheral blood mononuclear cells (PBMC) using specific primers for Interferon (IFN)-gamma, Interleukin (IL)-2, IL-4 and IL-10. Almost 63% of oral cancer patients showed polarization of a Th-like cytokine response as compared to 33% of the normal controls while 66.6% of normal controls showed a predominantly non-polarized Th0 response. Expression of IFN-gamma and IL-2 genes was more commonly seen in the early stage of the disease (p < 0.02) whereas majority of advanced stage tumours was associated with enhanced expression of IL-4 and IL-10 but not IFN-gamma and IL-2 genes. Patients with lymphnode metastases and poorly differentiated tumours expressed IL-4 and IL-10 more frequently with concomitant suppression of IFN-gamma and IL-2 genes. It seems therefore, that the development of oral squamous cell carcinoma leads to polarization of cytokine gene expression that is skewed towards the Th1-like response in the early stage. However, increasing tumour load and lymphnode invasion suppresses Th1 cytokine genes, thus skewing it toward a Th2-like cytokine response.