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In this study, we demonstrated that theophylline could inhibit NK cell activity in vivo. It should be noted that the concentration of theophylline that yielded the same amount of inhibition was lower in vivo than by direct addition in vitro. We suggested that long-term incubation causes strong suppression of the activities of individual NK cells, even at low concentrations of theophylline in vivo. The mechanism of this inhibition was not investigated in this study. Previous reports have shown that theophylline acts directly on NK cells by inducing intracellular elevation of cAMP via the inhibition of phosphodiesterase activity. There is a report demonstrating that polymorphonuclear cell functions can be inhibited by theophylline at therapeutic concentrations, and this is mediated by intracellular cAMP elevation. There are some reports concerning NK cells and human diseases (for review) and interaction with drugs. 16 I9*2i From the clinical point of view, inhibition of NK cell activity by theophylline at therapeutic concentrations would cause two important questions. First, we know that theophylline is a very effective drug for relief of bronchoconstriction; however, do we know whether it is clearly useful for prevention of asthmatic attacks, especially in steroid nondependent asthmatic patients?