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To define changes in sleep and subjective fatigue associated with localized radiation treatment, and to determine their relationship to interleukin-1B (IL-1), we prospectively followed 15 men, none of whom were depressed during 8 wk of radiation treatment for localized prostate cancer. Each patient rated fatigue daily on a visual analogue scale, recorded hours slept, and completed the Beck Depression Inventory weekly. Serum IL-1, taken at baseline and Fridays, was measured by quantitative enzyme immunoassay. Ranked weekly mean fatigue scores for each subject increased at week 4 (mean, 17 fractions, 1.8 Gy) then plateaued and rose in weeks 6 and 7. In week 6, the last week of full volume radiation, subjects slept most compared to all other weeks including week 7 when treatment was coned down. Ranked serum IL-1 tended to rise between weeks 1 and 4, as fatigue scores rose. These data suggest that localized radiation treatment is associated with increased fatigue and sleep requirement independent of depressive symptoms. Relative serum IL-1 changes may be one signal for the systemic reaction and subjective fatigue associated with the acute effects of radiation.