Common variable immunodeficiency (CVI) is a heterogeneous condition marked by a number of different immunologic defects. One group of patients, perhaps 60% of the CVI group as a whole, is characterized by T cells that produce reduced amounts of IL-2 (mRNA and protein product), IL-4, and IL-5 (mRNA) when stimulated with phytohemagglutinin. This defect does not extend to all lymphokines, however, because the cells produce normal amounts of interferon-gamma (mRNA and protein product) when exogenous IL-2 is present. Recently, we have reexamined the T cell lymphokine production defect using a panoply of T-cell activation stimuli and have shown that the defect is a subtle one that depends on activation of the cell via the CD3-T-cell receptor complex. Because T cells proliferate normally when stimulated via this receptor, this finding suggests the presence of a "downstream" defect, perhaps one involving the factors that are necessary for activation of lymphokine genes. A second form of CVI, in this case involving approximately 30% of the CVI group as a whole, is characterized by a reduced CD4/CD8 ratio and elevated numbers of CD8+ T cells bearing the CD57 marker. Although the CD4+ T cells in this patient group elaborate normal amounts of IL-2 under various activation conditions, their CD8+ T cells produce increased amounts of interferon-gamma. Furthermore, the CD8+ T cells in this case act as "suppressor" T cells, which suppress IgG production but not IgM production of purified (normal) SAC+, IL-2-induced B cells.(ABSTRACT TRUNCATED AT 250 WORDS)