Human growth hormone (GH) and insulin-like growth factor I (IGF-I) are known to bind to, and exert modulatory effects on, different immunocompetent cells, including CD16+/CD3- natural killer (NK) cells. NK cells are involved in various non-major-histocompatibility-complex-restricted actions of the immune system. Although no clinically significant defect in tumour or virus defence has been reported in GH-deficient patients, the data available indicate decreased NK cell activity in these patients. In most studies, the absolute number and percentage of NK cells have been found to be normal. Substitution with GH has been reported to normalize the decreased NK cell activity in GH-deficient patients. In a cross-sectional study in GH-deficient adults, decreased basal and interferon-beta (IFN-beta)-stimulated NK cell activity in vitro. Preliminary data on GH binding to NK cells indicate enhanced binding in GH-deficient patients when compared with normal controls.