Patients with head and neck squamous cell carcinoma (HNSCC) are biased toward the Th2 phenotype as they have increased levels of the Th2 cytokines IL-4, IL-6 and IL-10 and diminished levels of the Th1 cytokine IFN-gamma. However, this bias is incomplete since levels of the Th1 cytokines IL-2 and GM-CSF are increased. This study examined the interrelationship among the plasma levels of Th1 and Th2 cytokines in 101 HNSCC patients and 40 age-matched controls without a known malignancy. Control subjects showed extensive interrelationships among levels of IL-1, IL-2, IL-4, and IFN-gamma, as well as between GM-CSF and TGF-beta. HNSCC patients showed an interrelationship in levels of IL-2, IL-4, IFN-gamma and GM-CSF, but to a less significant degree. What was prominent was a decline in correlation among cytokine levels with increased disease burden, such that there were no relationships among any of the cytokines in stage T4 patients. Nodal involvement also was associated with cytokine levels being more independent of each other, although the impact of nodal disease was less prominent than tumor burden. These results show a partial Th2 cytokine bias in HNSCC patients and a progressively more aberrant expression of cytokines with more advanced disease.