There are close ties between stressful life experiences, mood disorders, substance abuse and sleep disturbances. Stressors have often been found to precede depressive episodes in humans.9 Studies in animals also show that stress can lead to depression-like behavior and sleep disruption with correlated changes in neural activity.10, 11 There is also evidence that both chronic stress and exposure to ethanol can have a far reaching impact on expression of circadian genes.12, 13 We have recently shown that prolonged restraint stress significantly upregulates expression of Dbp, Per1, Per2 and Per3 in multiple brain regions of C57BL/6J (B6) and DBA/2J (D2) inbred mouse strains.13 An important question then is whether or not natural variation in the expression of these genes also has a causal impact on stress and ethanol response in these mice?