Women have a higher prevalence of generalized anxiety disorder (GAD) than do men, but few studies have assessed gender differences in response to pharmacotherapy. In this study we examined gender as a correlate of response to 6 weeks of open, prospective fluoxetine treatment in 23 men and 22 women with a primary diagnosis of GAD. There was no difference by gender in age or prevalence of mood and anxiety comorbidity; however, GAD onset occurred at a significantly younger age in women compared with men. Despite a lack of difference in baseline severity measures, women had a significantly poorer response to fluoxetine as measured by both the Hamilton Anxiety Rating Scale (HAM-A) and Clinician Global Impression-Severity Scale (CGI-S). In multivariate analyses, there was a significant interaction between age of onset and gender: men with younger age of onset and women with older age of onset exhibited poorer response on the HAM-A. These data, though limited in sample size and by the post hoc nature of our analyses, offer preliminary support that women with GAD, particularly those with a later age of onset, may have a poorer response to the selective serotonin reuptake inhibitor (SSRI) fluoxetine. Larger placebo-controlled trials are needed to more definitively examine gender and treatment response in anxiety disorders.