Absolute and relative NK cell numbers were determined in peripheral whole blood by flow cytometry in patients with common variable immunodeficiency (CVID) (n = 55) and X-linked agammaglobulinaemia (XLA) (n = 19) on regular immunoglobulin (IVIG) therapy. Absolute CD3-CD16+ NK cell numbers were significantly reduced in CVID patients (median 108/microl, range 23-815), compared with normal subjects (n = 60) (289/microl, range 56-640, P < 0.001). Total lymphocyte concentrations were significantly lower in CVID (median 1587/microl, range 523-7519) compared with normal subjects (median 2019/microl, range 1124-3149, P = 0.004), with the percentage of NK cells also being significantly decreased (median 7.5%, range 3.0-33. 0%, compared with 14.2%, range 2.6-30.8%, P < 0.001). In XLA, absolute NK cell numbers (median 140/microl, range 32-551, P < 0. 001) but not relative numbers were significantly reduced compared with normal controls. We excluded the possibility that IVIG interferes with in vitro binding of CD16 MoAbs. Further analysis of NK cell subsets showed a deficiency of both CD16+ and CD56+ cells in CVID, most marked in the CD3-CD8dim subpopulation, which may be due to increased homing of these cells to the gut. Serial studies on a small number of patients suggest that IVIG therapy has no short-term effect on NK cells, although we cannot exclude an effect with prolonged use. Although there are no obvious clinical effects of the NK depletion in CVID and XLA, this may be a factor in their predisposition to cancer.