Perceptual asymmetries as indicated by dichotic listening tasks have been associated with both subtype of depression and response to antidepressant treatment. To examine the association between this relatively new measure and more traditional measures of hypothalamic-pituitary-adrenal axis (HPA) activation in depression, we assessed perceptual asymmetry and basal plasma cortisol in a sample of depressed outpatients undergoing a double-blind, placebo-controlled medication trial. Each measure was examined for its ability to predict response to treatment. Perceptual asymmetry was significantly associated with plasma cortisol levels, and was also a significant predictor of treatment response. The association between plasma cortisol and treatment response did not reach significance. Our findings are limited by relatively small sample sizes but encourage further examination of perceptual asymmetry measures as predictors of treatment response and in relation to HPA activation in depression.