The present study, including 81 depressive patients, compares the prophylactic efficacy of lithium and amitriptyline in recurrent unipolar depression over a treatment period of 2.5 years in a randomised multicentre design. Hospitalisation, re-emergence of depressive or subdepressive recurrences, unwanted side-effects and need of concomitant psychotropic medication were considered to indicate treatment failures. Average dosage for amitriptyline was 98 +/- 37 mg/day, average lithium blood level was 0.59 +/- 0.12 mmol/l. Survival analyses demonstrated a significant superiority of lithium (P = 0.015) regarding the outcome criteria 'recurrences and/or subclinical recurrences' and non-significantly better results of lithium compared to amitriptyline concerning 'recurrence' (P = 0.059) or 'recurrence and/or concomitant medication' (P = 0.066).