The similarities and differences in the clinical response and incidence of adverse symptoms between zimeldine and amitriptyline have been evaluated by use of a combined analysis of four double-blind clinical trials in depression. In total, 197 patients were included in this series of studies. The efficacy of the drugs was assessed using the Hamilton Rating Scale for Depression (HAM-D). Reports of adverse symptoms were actively elicited by use of a check-list of symptoms and rated for severity. The overall clinical efficacy of the two drugs was shown to be equivalent with a high degree of statistical confidence. However, there exist differences in the profile of action. Amitriptyline has a significant advantage in insomnia problems. In spite of this zimeldine was shown to be at least as effective as amitriptyline in reducing anxiety. Amitriptyline is associated with significantly more anticholinergic side-effects, whereas headache is more disturbing during zimeldine treatment. The combination of several independent trials based on similar protocols can be a useful tool to increase the statistical reliability of conclusions relative to that which can be achieved in standard sized, individual studies in depression.