OBJECTIVE: The primary aim of this article is to describe sexual concerns in postpartum women with DSM-IV diagnoses of major depressive disorder (MDD) before and during treatment with antidepressants in an 8-week double-blind randomized trial. METHOD: Seventy women aged 19-42 years participated and were randomly assigned to either the tricyclic antidepressant nortriptyline (N = 38) or the serotonin selective reuptake inhibitor sertraline (N = 32). Women completed the Arizona Sexual Experience Scale to evaluate sexual concerns at enrollment and weekly during the trial. The outcome measure for depression, Hamilton Rating Scale for Depression, was completed in clinical interviews at the same time points. Comparisons of demographic and other characteristics of women were completed with t tests for continuous measures and with chi(2) or Fisher exact statistics for categorical measures. Mixed-effects regressions were used to test for significance of the main effects of depression symptom scores, drug assignment, weeks treated with medication, and the interactions of these variables. Data were collected from April 1997 to April 2002. RESULTS: At entry into the randomized trial, 73% (N = 51) of the women reported problems in 3 or more areas of sexual concern compared to 37% (N = 26) at week 8. There were no significant differences at study entry in women randomly assigned to nortriptyline compared to those randomly assigned to sertraline in summary scores of sexual function nor in specific sexual concerns at any time point. At week 8, women whose MDD remitted were more likely to report fewer (< 3) sexual concerns than women whose MDD did not remit (76% vs. 24%, p = .006), independent of drug assignment. CONCLUSIONS: In postpartum women, sexual concerns are primarily affected by remission of depression rather than side effects of either a tricyclic or serotonergic antidepressant.