Cullin-5 (cul-5), a member of the cullin gene family, may have a role in proteolysis and cell cycle regulation. Our recent study demonstrated that cul-5 mRNA is ubiquitously expressed in the central nervous system and many peripheral organs. The present study used quantitative realtime polymerase chain reaction to measure changes in cul-5 mRNA expression as a consequence of osmotic stress in vivo. Cul-5 mRNA levels were significantly increased in the rat cerebral cortex, hypothalamus and kidney following 48 h of water deprivation. Water deprivation for a shorter time period (24 h) or rehydration (24 h access to water following 48 h of water deprivation) also elevated kidney cul-5 mRNA levels. Water deprivation did not significantly alter cul-5 mRNA levels in the brainstem, cerebellum, hippocampus, lung or liver. Since cul-5 appears to be linked to proteosome-mediated protein degradation, it may have a role in protein regulation under conditions of osmotic stress.