The clinical efficacy of a treatment with clomipramine (150 mg/day) associated with a daily dose of 50 micrograms of LT3 (CMI + LT3) compared to a treatment with clomipramine (150 mg/day) (CMI + placebo) for a period of 42 days has been examined in a pilot study, randomized in double-blind conditions, including 20 patients with a normal thyroid status, but presenting a major depressive syndrome (DSM III). The minimum including score was 30 on the Montgomery Asberg Scale (MADRS). The patients were considered as remitted when the MADRS-score was < or = 10. After 28 days of treatment, the efficacy of CMI + LT3 was found to be superior to CMI + placebo (p < 0.05). Side effects (CHESS 84) were those generally described for tricyclic antidepressants (constipation, dry mouth, lipothymia, tremor). Patients of the CMI + LT3 group experienced a slight hyperthyroidism. The determination of the plasma levels of CMI and desmethylclomipramine (DCMI) showed the presence of three non-compliant patients, but also that there was no relationship between plasma levels and clinical efficacy of the drug. Significant correlations were found between CMI and DCMI levels on day 14 compared with those of day 28 and 42, respectively. LT3 was without effect on the plasma levels of CMI and DCMI.