BACKGROUND: Studies on gender differences in depression have usually included a mixture of patients with first-episode, chronic and recurrent depression. Consequently, the results might be confounded by the history of depression among participants. The present study evaluated gender differences in sociodemographic, clinical and treatment variables among patients suffering exclusively from single-episode depression. METHOD: Systematic recruitment of 301 participants via the Danish Psychiatric Central Research Register and assessment by means of questionnaires and interviews regarding psychiatric diagnoses, personality traits and disorders, stressful life events, family history, and treatment response. RESULTS: Female patients showed a higher level of neuroticism and more residual anxiety symptoms after treatment of the depression. There were no gender differences in severity of depression, psychiatric co-morbidity (including personality disorders), stressful life events prior to onset, family loading of psychiatric disorders, or treatment outcome. CONCLUSION: The results provide evidence for a higher level of anxiety and neuroticism among females with a recent onset of depression, whereas other clinical characteristics of first-episode depression were equivalent between male and female patients. Only patients with contact to a psychiatric hospital were included; thus, the results cannot be generalized to patients in primary care.