BACKGROUND Diurnal mood variation (DMV) with early morning worsening is considered a classic symptom of melancholic features of major depressive disorder (MDD) according to the Diagnostic and Statistical Manual. This report used data from the sequenced treatment alternatives to relieve depression study to determine whether DMV was associated with treatment outcome to citalopram. METHODS Two thousand eight hundred and seventy-five outpatients with nonpsychotic MDD were evaluated during a 14-week trial of the selective serotonin reuptake inhibitor citalopram. Participants were divided into three groups: those with "classic" DMV (early morning worsening), those with any form of DMV (morning, afternoon, or evening worsening), and those with no DMV. Participants with classic DMV and those with any form of DMV were compared to those with no DMV in terms of baseline sociodemographic and clinical characteristics, treatment outcomes, and treatment features. RESULTS Minor baseline clinical characteristics and treatment feature differences were found between participants with and without DMV. Participants with classic morning DMV had slightly higher response rates than those without DMV. However, no differences were found in response or remission between either group of participants with DMV and those with no DMV. CONCLUSIONS DMV does not appear to be associated with a unique prominent pattern of response to selective serotonin reuptake inhibitor treatment in patients with depression, and does not appear to be a serotonergically modulated process. Further evaluation is necessary to determine if this relationship holds true for dopaminergic and noradrenergic antidepressant agents, such as dual-acting agents or antidepressant medication combinations.