<jats:sec id="S003329171700112X_sec_a1"><jats:title>Background</jats:title><jats:p>Females are more likely than males to develop major depressive disorder (MDD). The current study used fMRI to compare the neural correlates of autobiographical memory (AM) recall between males and females diagnosed with MDD. AM overgenerality is a persistent cognitive deficit in MDD, the magnitude of which is correlated with depressive severity only in females. Delineating the neurobiological correlates of this deficit may elucidate the nature of sex-differences in the diathesis for developing MDD.</jats:p></jats:sec><jats:sec id="S003329171700112X_sec_a2" sec-type="methods"><jats:title>Methods</jats:title><jats:p>Participants included unmedicated males and females diagnosed with MDD (<jats:italic>n</jats:italic> = 20/group), and an age and sex matched healthy control group. AM recall in response to positive, negative, and neutral cue words was compared with a semantic memory task.</jats:p></jats:sec><jats:sec id="S003329171700112X_sec_a3" sec-type="results"><jats:title>Results</jats:title><jats:p>The behavioral properties of AMs did not differ between MDD males and females. In contrast, main effects of sex on cerebral hemodynamic activity were observed in left dorsolateral prefrontal cortex and parahippocampal gyrus during recall of positive specific memories, and middle prefrontal cortex (mPFC), and precuneus during recall of negative specific memories. Moreover, main effects of diagnosis on regional hemodynamic activity were observed in left ventrolateral prefrontal cortex and mPFC during positive specific memory recall, and dorsal anterior cingulate cortex during negative specific memory recall. Sex × diagnosis interactions were evident in the dorsomedial prefrontal cortex, caudate, and precuneus during positive memory recall, and in the posterior cingulate cortex, insula, precuneus and thalamus during negative specific memory recall.</jats:p></jats:sec><jats:sec id="S003329171700112X_sec_a4" sec-type="conclusion"><jats:title>Conclusions</jats:title><jats:p>The differential hemodynamic changes conceivably may reflect sex-specific cognitive strategies during recall of AMs irrespective of the phenomenological properties of those memories.</jats:p></jats:sec>