Platelet serotonin (5-HT) and plasma tryptophan (free and total) levels were measured in 25 unmedicated depressed patients and in 25 age- and sex-matched healthy controls. The same parameters were determined in the patients after 3 weeks and 2 months of imipramine treatment. Comparisons between patients and control values showed a significant decrease in total plasma tryptophan and platelet 5-HT in unmedicated patients. During treatment, the clinical condition of the patients improved, while plasma tryptophan and platelet 5-HT values normalized after 3 weeks and 2 months, respectively. Clinical status, plasma tryptophan, platelet 5-HT, as well as other biological parameters determined concurrently in the patients, such as platelet monoamine oxidase (MAO), 5-HT uptake, and imipramine binding were compared in search of significant correlations: neither the individual values of any of them nor the magnitude of their changes at any given stage or interval of the study, respectively, were found significantly correlated. These results suggest that a series of 5-HT-related biological parameters are altered in endogenous depression and tend to normalize with imipramine treatment leading to clinical recovery. Within individuals, those parameters are not correlated, suggesting that both the effect of the drug and clinical improvement affect them separately.