The inbred C57BL/6 mouse strain is known to prefer an ethanol solution in a two-bottle choice procedure, whereas the inbred DBA/2 mouse strain avoids drinking ethanol in this paradigm. The genetic basis of this behavior is still unclear but the endogenous opioid system is one of the factors thought to be involved. Therefore, we were interested to see if there are basal differences between the two lines of mice in the kappa opioid receptor (kappa OR) mRNA content in different brain regions. Because of the low expression level of this gene and the limited amount of tissue we developed a sensitive competitive reverse transcription-polymerase chain reaction (RT-PCR) assay for evaluation of levels of kappa OR mRNA in brain tissue. In septum and hypothalamus the DBA/2 mice showed a significantly higher basal level of kappa OR mRNA than did C57BL/6 mice. It is suggested that a difference in basal amount of kappa OR mRNA among these strains could lead to differences in kappa OR activity and subsequently to variations between the strains in distinct behaviors such as in ethanol preference.