The aim of this study was to determine whether the apolipoprotein E genotype differs in patients who respond or do not respond to electroconvulsive therapy (ECT). Inpatients, outpatients, and day-treatment patients who had received ECT comprised the study group. The 34 patients included met DSM-III-R criteria for affective or schizoaffective disorder. Responder or nonresponder status was assessed using the Clinical Global Inventory and Montgomery Asberg Depression Rating Scale. Blood samples were taken and coded when the patients entered the study. DNA extraction and apolipoprotein E genotyping were performed with no knowledge of the clinical classification of the patients. A significant difference in E4 genotype distribution was found between ECT responders and nonresponders (p < 0.02); psychosis was significantly less frequent in this group (p = 0.046), and there was a trend toward older onset of depression among these persons (p = 0.10). Only the E3/3 genotype was found in the patients with early-onset depression. The E4 genotype appears to define a subgroup of patients with late-onset depression who respond to ECT. If confirmed in prospective studies, this may provide a useful marker in the treatment decision-making process for late-onset depression.