The purpose of this investigation was to reexamine the relationship between self-reported depression and laterality of temporal lobe epilepsy and to determine the contribution of associated frontal lobe dysfunction in predisposing patients to depression. Sixty-four patients with complex partial seizures of left (n = 26) or right (n = 38) temporal lobe origin were administered several self-report measures of mood state (Beck Depression Inventory, Center for Epidemiological Studies-Depression scale, Beck Anxiety Inventory), and a test of frontal lobe function [Wisconsin Card Sorting Test (WCST)]. There were no overall differences between the left and right temporal lobe groups on the measures of depression and anxiety. However, the left temporal lobe group exhibited a significant relationship between the degree of associated frontal lobe dysfunction (as indicated by increased perseverative responding on the WCST) and dysphoric mood state. For the right temporal lobe group there was a nonsignificant inverse relationship between mood state and indices of frontal lobe dysfunction. These results (1) are consistent with the broader psychiatric literature, which has implicated a relationship between depression and left frontal lobe dysfunction, (2) suggest that previous conflicting reports of depression/left temporal lobe epilepsy relationships are due in part to variations in the intactness of frontal lobe function, and (3) suggest that the presence of associated frontal lobe dysfunction may be a consideration in understanding interictal psychopathology in epilepsy.