The aim of this study was to examine response and remission rates in outpatients treated with sertraline or fluoxetine who were suffering from two depression subtypes: anxious-depression and severe depression. Data were pooled from five double-blind studies comparing fluoxetine versus sertraline for the treatment of DSM-III-R or IV major depression. Clinical outcome was assessed using the Hamilton Depression Rating Scale (HAM-D) and the Clinical Global Impression-Improvement scale (CGI-I). One thousand and eighty-eight patients were randomized, with 654 (60%) meeting criteria for anxious depression and 212 (19%) meeting criteria for high severity depression. For the total sample, treatment response was similar for both sertraline and fluoxetine. In the high severity subgroup, the mean (+/-SD) HAM-D score at week 12 was 8.9+/-5.7 for sertraline and 10.8+/-6.9 for fluoxetine (P=0.07), and the mean (+/-SD) CGI-I score was 1.5+/-0.7 for sertraline and 2.0+/-1.1 for fluoxetine (P=0.005). CGI-I responder rates were 88% versus 71% (P=0.03) in the high severity subgroup, and 84% versus 79% (P=0.16) in the anxious-depression subgroup. Overall, sertraline and fluoxetine showed comparable antidepressant efficacy, although sertraline may offer an advantage in those patients with severe depression.