Depression and severity of depressive symptoms have been associated with alterations of cell-mediated immune function. Sleep disturbance might play a role in the reduction of NK activity since severity of insomnia has been found to be a distinct correlate of reduced NK activity in depressed patients separate from the contribution of other depressive symptoms. Furthermore, a reduction of NK activity has also been found in persons undergoing marked adversity who report insomnia but no other symptoms of depression. Despite these clinical data that suggest a distinct association between reduced natural cytotoxicity and insomnia, no study has yet tested whether objective assessments of sleepwake activity might be associated with alterations in immune function, even though it is well recognized that objective sleep EEG measurement is a more reliable assessment of sleep than self reports of insomnia. Our recent preliminary work involving measurement.of EEG sleep suggests that disturbances of sleep continuity, sleep architecture, and REM sleep are indeed correlated with reduced cytotoxicity. In addition, plasma levels of IL-2 have been found to mediate the association between depressive symptoms and NK activity in depressed patients. Finally, consistent with previous findings, nocturnal secretion of IL-2 has been found to occur in sleeping subjects. This research will be extended by the following aims: 1) to establish further the relationship between-sleep-wake activity and natural killer cytotoxicity; 2) to characterize the role of sleep activity in the secretion of lymphokines; 3) to examine whether the nocturnal secretion of IL-1 and IL-2 mediates the association between sleep disturbance and altered NK activity. In summary, the findings of this study have the potential to demonstrate that sleep-wake activity has a role in mediating cellular immunity, further implicating nocturnal secretion of immune response modifiers as an underlying mechanism that links sleep alterations and disturbed immune function.