The authors studied CD40 ligant (CD40L) expression and interleukin-10 (IL-10) production in 16 patients with common variable immunodeficiency (CVI). Mean CD40L expression, determined by using cytofluorimetry, and measured as the mean fluorescence intensity following stimulation of peripheral blood mononuclear cells (PBMC) with phorbol myristate acetate (PMA) and calcium ionophore in 12 patients, was comparable to that of controls. However, three CVI patients showed fluorescence intensity in stimulated cells below 2 standard deviations of normal donors' mean and two other patients had only a slight increase of stimulated versus unstimulated cells (< 10 channels). IL-10 production after stimulation of PBMC with both anti-CD3 or anti-CD3 plus PMA gave similar results in CVI patients and normal controls. In vitro stimulation of PBMC with anti-CD40 and various combinations of cytokines (IL-2, IL-4 and IL-10) induced IgG production above 100 ng/ml in one CVI patient out of 13 tested. The data suggest that alterations of IL-10 production are unlikely to play a major role in the pathogenesis of impaired IgG production in most CVI patients. CD40L appears to be normally expressed in two thirds of CVI patients, but it may be functionally defective.