Numerous studies have shown that acute microwave exposure causes cognitive deficits in animals, possibly via hyperthermia, but the biological effect of microwave exposure on memory processing is still unknown. The release of adenosine is demonstrated to be a general way for the cells to respond to metabolically stressful conditions such as hypoxia and ischemia. The present study aimed to examine whether adenosine mediates biological effects of microwave exposure on memory processing using a continuous multiple-trial inhibitory avoidance task. Results demonstrated that microwave exposure for 20 min before training impaired memory acquisition and retention performance in mice, assessed by the number of training trials and by latency to enter the dark compartment. The mice exposed to microwave radiation showed a dose-dependent hyperthermia. Moreover, the cell numbers of hippocampus were decreased in the mice receiving microwave exposure at an average power density of 50 mW/cm(2), indicating the anatomical correlation to hippocampal-amygdaloid structures corresponding with the memory disrupt of the mice. Administration of theophylline, a nonspecific adenosine receptor antagonist, 30 min before microwave exposure, completely antagonized the impairment of inhibitory avoidance acquisition but not retention. These results suggest that the adenosine regulation pathway was partially involved in microwave-induced impairment of inhibitory avoidance memory.