This study was designed to determine the possible effects of omeprazole on human natural killer cells. Peripheral venous blood samples were taken from 20 peptic ulcer patients before and at the 14th and the 28th days of omeprazole treatment. Mononuclear cells were removed from blood and their capability of making conjugation with K562 target cells and lysing K562 target cells was evaluated. A significant decrease was found (P < 0.001) in the 14th and the 28th days compared with the basal value of the capability of the mononuclear cells to conjugate with the K562 target cells and to lyse them. This study demonstrated that omeprazole significantly reduces natural killer cell functions. This finding suggests that omeprazole may also have some effects on the other systems in addition to parietal cell acid secretion.