The effect of a chronic morphine treatment on prodynorphin gene expression has been studied. Morphine has been intraperitoneally administered twice daily for seven days into rats. RNAs from hippocampus and striatum have been extracted and analyzed with probes complementary to the prodynorphin mRNA. A marked reduction in mRNA levels was detected in hippocampus, following chronic morphine treatment; in striatum results showed either a slight decrease or no substantial changes in mRNA levels. These results indicate that the chronic morphine is able to induce modifications in the homeostasis of the endogenous opioid gene expression, at least in some areas of the rat brain. In addition, our data support the hypothesis that a tolerance to opiates might involve alterations in functions of brain pathways which utilize the opioid peptidergic system.