In this study, the effects of chronic ethanol treatment on inositol 1,4,5-tris-phosphate (IP3) and inositol 1,3,4,5-tetrakisphosphate (IP4) specific binding in rat brain was investigated. In the cerebellum, chronic, but not acute, ethanol treatment caused a decrease in the number of IP3 receptors. The effect of chronic ethanol treatment on IP3 and IP3 receptor mRNA levels was also studied in order to determine the mechanisms responsible for the decrease in IP3 receptor binding. Chronic ethanol treatment did not change IP3 levels, indicating that the decrease of IP3 receptors is not caused by the alteration of IP3 levels. Also IP3 receptor mRNA levels had no change after chronic ethanol treatment. These findings suggest that the decrease in IP3 receptors in the cerebellum could be caused by either a decrease in the translation of IP3 receptor mRNA or an increase in proteolysis of IP3 receptors. In contrast, chronic ethanol treatment had no effect on the Bmax or Kd of IP4 specific binding in the cerebellum. It is speculated that a change at the level of the IP3 receptor in the cerebellum may be associated with the development of adaptation and tolerance to chronic ethanol exposure.