The influence of various doses of caffeine and theophylline on analgesic effect of morphine was tested in mice and rats in the hot plate and tail immersion tests. Caffeine in rats potentiated the morphine analgesia in both tests in a dose-dependent manner. In mice the caffeine-morphine interaction was biphasic: lower caffeine doses (10 and 25 mg/kg) inhibited, while higher (75 and 100 mg/kg) potentiated the analgesic effects of morphine. Theophylline interacted with morphine in a manner similar to that of caffeine.