There is evidence that sweeteners such as sucrose and saccharin interact with endogenous opioid systems. Further research has shown that feeding different concentrations of sucrose and saccharin alter latency in the tail-flick test. In this study, the influence of a 12-day regimen of different sweetening agents, sucrose (32%), saccharin (0.08%) and aspartame (0.16%) on morphine-induced analgesia in the formalin test was investigated. Male albino mice (20-27 g) were used for the experiments. The animals were given 12 days to adapt to the dietary conditions. An initial subcutaneous injection of saline or morphine (1.5, 3, 6 or 9 mg/kg) was given 30 minutes before the observation period. Recording of the early phase began immediately and continued for 10 minutes. Recording of the late response began 20 minutes after injection and continued for 10 minutes. Sucrose and aspartame increased the analgesia of morphine in the early phase while saccharin had no effect. On the other hand saccharin and sucrose decreased the effect of morphine in the late phase while aspartame increased the effect of morphine-induced analgesia. In conclusion, the present data provide further evidence for an important role of dietary variables in determining the effects of exogenous opioids on pain sensitivity.