The prevalence of subjective side-effects was studied in 258 control subjects, 65 drug-free depressive in-patients and 94 lithium-treated out-patients. It was shown that drug-free depressives reported more side-effects than both control subjects and lithium-treated patients. Side-effects were studied during amitriptyline therapy. Depressed patients on no medication complained of only slightly fewer side-effects than when they had received amitriptyline. There was a significant positive correlation of Hamilton depression scores and side-effects scores at baseline. Side-effects and affective morbidity over two years were investigated in 94 patients with recurrent affective disorders on long-term lithium therapy. Psychological variables were also investigated in 74 of these patients. Subjective side-effects reported by lithium-treated patients including those specific to lithium were related to their affective morbidity and personality variables. Patients on lithium complained significantly less of headache and unilateral headache than controls.