Despite the wide variance in therapeutic response to antidepressants, there are few clinical or biological predictors of treatment outcome. Studies have suggested the possible value of dichotic listening measures of perceptual asymmetry (PA) as predictors of treatment response. This study examined the relation between outcome of fluoxetine treatment and performance on verbal and nonverbal dichotic tests. As part of a multisite study, 86 outpatients with major depression were tested on dichotic fused-words and complex-tones tests both before and during treatment. Fluoxetine responders differed from nonresponders in having greater right-ear (left-hemisphere) advantage for dichotic words and less left-ear (right-hemisphere) advantage for complex tones. There was no change in PA during fluoxetine treatment, which indicates that PA differences between treatment responders and nonresponders are stable (trait) characteristics. An aggregate, characteristic PA measure was the best predictor of responder status in a logistic regression analysis. Findings from two clinical centers support the hypothesis that a characteristic tendency for relatively greater left-than right-hemispheric activation during dichotic listening is associated with better outcome of fluoxetine treatment.