Mice of the BALB/c, C57BL/6, and CBF1 strains were studied with respect to analgesic activity of and physical dependence on morphine. The acute administration of morphine resulted in analgesic response in the three strains with the following ranking orders: BALB/c greater than C57BL/6 = CBF1 for 5 mg/kg, and C57BL/6 greater than BALB/c greater than CBF1 for 10 and 20 mg/kg. Mice were treated with morphine-admixed food (1-3 mg/g of food) for 9 days. During the treatment, morphine intake in BALB/c was lower than those in C57BL/6 and CBF1. Thus, we examined the degree of physical dependence in three mouse strains after chronic morphine injections for 10 days. There was significant difference in naloxone-precipitated body weight loss among strains, the ranking being as follows: BALB/c greater than CBF1 greater than C57BL/6. However, there was no difference in appearance rate of naloxone-precipitated jumping, but a difference in body shakes and body weight loss, among strains. These results suggest that analgesia of and preference for morphine, and naloxone-precipitated weight loss and body shakes may be influenced by genetic factors.