A number of phenotypic and functional alterations have been described in T cells of cancer patients. These changes are believed to reflect an impaired T-cell mediated immunity, which in turn, may result in a decreased capacity to generate an effective antitumor response. Several mechanisms have been proposed to explain depressed immunity in cancer patients including tumor-derived suppressor factors, abnormal cytokine production, deletion or inactivation of tumor-reactive T-cells. To investigate the mechanism underlying the immunodeficiency in Hodgkin's disease (HD) we studied the expression of T cell receptor zeta chain, which plays a vital role in the cascade of events leading to T and NK cell activation. The expression of the zeta chain of the T cell receptor/CD3 complex was analyzed by dual colour immunofluorescence on peripheral blood T lymphocytes: CD3+, CD4+, CD8+ and NK-cells (CD56+) in patients in different phases of the disease. Zeta chain was significantly reduced on CD3, CD4, CD8, and CD56 positive cells from patients in active phase of the disease compared with normal controls (p=0.05). In patients tested in complete clinical remission the values were normal except for the subpopulation of CD8+ cells in which the expression of zeta chain remained significantly reduced compared with controls. Downregulation of CD3/zeta-chain in PBLs and NK cells in active phase of HD- and to a lesser extent in clinical remission may contribute to immunodeficiency associated with the disease.