Major depressive disorder (MDD) is associated with poor problem-solving abilities. In addition, certain personality disorders (PDs) that are common among patients with MDD are also associated with limited problem-solving skills. Attempts to understand the relationship between PDs and problem solving can be complicated by the presence of acute MDD. Our objective in this study was to investigate the relationships between PDs, problem-solving skills, and response to treatment among outpatients with MDD. We enrolled 312 outpatients with MDD in an open, fixed-dose, 8-week fluoxetine trial. PD diagnoses were ascertained via structured clinical interview before and after fluoxetine treatment. Subjects completed the Problem-Solving Inventory (PSI) at both time points. We used analyses of covariance (ANCOVAs) to assess relationships between PD diagnoses and PSI scores prior to treatment. Subjects were divided into three groups: those with PD diagnoses that remained stable after fluoxetine treatment (N=91), those who no longer met PD criteria after fluoxetine treatment (N=119), and those who did not meet criteria for a PD at any time point in the study (N=95). We used multiple chi(2) analyses to compare rates of MDD response and remission between the three PD groups. ANCOVA was also used to compare posttreatment PSI scores between PD groups. Prior to fluoxetine treatment, patients with avoidant, dependent, narcissistic, and borderline PDs reported significantly worse problem-solving ability than did patients without any PDs. Only subjects with dependent PD remained associated with poorer baseline problem-solving reports after the effects of baseline depression severity were controlled. Patients with stable PD diagnoses had significantly lower rates of MDD remission. Across PD groups, problem solving improved as MDD improved. No significant differences in posttreatment problem-solving were found between PD groups after controlling for baseline depression severity, baseline PSI score, and response to treatment. Treatment with fluoxetine is less likely to lead to remission of MDD in patients with stable PDs. More study is needed to investigate causal links between PDs, problem solving, and MDD treatment response.