SUMMARYWe investigated the expression of T helper (Th)1/Th2 regulatory cytokine receptors on lymphocytes from patients with common variable immunodeficiency (CVID), a disorder associated with raised Th1 cytokine production, comparing the results with those from healthy individuals and atopic asthmatics, the latter generally considered to have a Th2-driven disease. We proposed that alterations in some of the relevant receptors might be related to the observed imbalances in Th1/Th2 cytokines. Cells from CVID patients showed an increase in the percentages of CD212 [interleukin (IL)-12R β 1] cells within the CD4 + CD45RA + and CD8 + CD45RA + subsets (24% and 41%, respectively), as compared to CD4 + CD45RA + and CD8 + CD45RA + in healthy subjects (6% and 23%, respectivey). Approximately 21% of the CD4 + CD45RA + naïve cells expressed IL-18R α , compared with 11% in healthy subjects. In contrast, the cytokine-receptor expression in asthmatics was similar to that of controls. In spite of the above differences, after 72 h of stimulation with anti-CD3 and anti-CD28, cytokine receptor up-regulation was similar in all three groups, with up to 80% of both CD45RA + and CD45RO + lymphocytes expressing CD212 (IL-12R β 1) and IL-18R α . Approximately 50% of the 'naïve', and 25% of the 'memory' subpopulations up-regulated IL-12R β 2. These findings provide further evidence of a polarization towards a Th1 immune response in CVID, the mechanism possibly involving up-regulation of IL-12-mediated pathways.