The effect of chronic lithium treatment on morphine-induced analgesia was studied in a time-dependent manner in old mice. All mice received lithium chloride via drinking water of 600mg/l for three weeks. Both basal pain sensitivity and morphine-induced analgesia were determined with a hot-plate test before and after chronic lithium drinking at six different times of the day every four hours. Chronic lithium exposure did not cause any significant change in basal pain sensitivity but the circadian rhythm of morphine analgesia disappeared in old mice. These findings suggest that biological rhythms may alter pharmacokinetic and pharmacodynamic properties of drugs and conversely drugs may alter the rhythmic properties of biological functions. Thus, administration time of drugs should be considered in both experimental designs and clinical settings.