Activation of T cells after ligation of the antigen-specific T-cell receptor initiates a cascade of metabolic and biochemical alterations that culminate in cell proliferation. The major changes include a series of phosphorylation reactions on numerous protein substrates, phosphatidylinositol hydrolysis, intracellular Ca2+ accumulation, gene activation, lymphokine receptor expression, and lymphokine secretion. Despite a great deal of work unraveling the structure of the T-cell receptor complex and the many biochemical events triggered by ligation of the T-cell receptor, the exact link between the various responses is not entirely defined. Nevertheless, abnormalities in any of these initial events may be presumed to have an impact on signal transduction, thereby resulting in a T-cell immunodeficiency. Such defects may be restricted to certain T-cell subsets or functions or represent more global defects.