Mild-intensity whole-body hyperthermia was induced using a Heckel 2000 device, which uses water-cooled infrared lamps to heat the body (Heckel Medizintechnik GmbH, Esslingen, Germany). Using the Centers for Epidemiologic Studies Depression Scale (CES-D) (2), we found that a single session (mean session time, 126.7 minutes [SD=18.0]) induced a rapid, robust, and sustained reduction in depressive symptoms (CES-D score before treatment, mean=29.9 [SD=10.6]; 5 days after treatment, mean=19.2 [SD=12.3]; t=4.53, df=15, p<0.001, effect size=1.13). Thirteen of these patients received no other pharmacologic or psychotherapeutic intervention during the 5 days following whole-body hyperthermia, whereas three patients were being chronically treated with a selective serotonin reuptake inhibitor (SSRI), with no change in dosage during the study period. Interestingly, when examined separately, whole-body hyperthermia appeared to have no effect in the three individuals receiving SSRI treatment. With these three individuals removed from analysis, the effect size of the hyperthermia increased (t=5.15, df=12, p<0.001, effect size=1.4).