In this study, 16 patients with obsessive-compulsive disorder (OCD) who had partially improved during at least 6 months of treatment with clomipramine were sequentially treated with triiodothyronine and lithium carbonate in an 8-week double-blind cross-over study. Both triiodothyronine and lithium carbonate have been reported to be efficacious in open trials as adjunctive agents when combined with tricyclics in the treatment of OCD and depressed patients. However, in our controlled study, OCD and depressive symptoms, as assessed by standardized rating scales in the patient group as a whole, did not significantly change after either adjuvant treatment. Further analysis on an individual patient basis revealed that neither adjuvant medication was associated with a clinically meaningful change (greater than 25%) in OCD symptoms. However, lithium, but not triiodothyronine, adjuvant therapy was associated with a 25% or greater reduction in depression scores in 44% of the patients. This controlled study lends further support to the contention that OCD may represent a disorder with characteristics distinct from affective disorders.