We examined the effects of single and repeated stress on the expression of interleukin-6 (IL-6) and IL-6 receptor (IL-6R) mRNAs in the rat midbrain and hypothalamus using reverse transcriptase-polymerase chain reaction (RT-PCR). Following a single episode of restraint stress for 4 hours (1R) or 4 hours per day on two (2R) or three (3R) consecutive days, the hypothalamus and midbrain were removed immediately and the levels of IL-6 and IL-6R mRNAs in both regions were determined. Regional differences in stress-related changes in mRNA levels were noted. The expression of IL-6 mRNA in the hypothalamus did not change in 1R group but decreased in 2R and 3R groups. The expression of IL-6R mRNA in the same region significantly diminished in all groups. In the midbrain, the expression of IL-6 mRNA increased in 1R group and decreased in 2R and 3R, while the expression of IL-6R mRNA significantly diminished in 1R and 3R groups but was not different from control in 2R group. Our findings indicate that repeated stress in rats produce changes in IL-6 and IL-6R mRNAs in the midbrain and hypothalamus that are different than those of a single stress episode.