Previous studies have suggested that chronic treatment with tricyclic antidepressants alters brain NE turnover. This action is more likely a biochemical correlate of their clinical effect than is the blockade of amine reuptake, because the latter occurs with acute administration, whereas tricyclics must be given chronically for clinical improvement. In this paper the effects of chronic treatment with the tricyclics desmethylimipramine (DMI) and iprindole (a clinically effective tricyclic that does not potently block amine reuptake) on rat brain NE turnover, as measured by the Conversion Index, was studied. Chronic DMI, but not iprindole, decreased NE turnover. These results are discussed regarding the proposed mechanism of action of tricyclics and the 'catecholamine hypothesis of affective disorders'. Chronic DMI also tended to decrease endogenous brain NE, and chronic treatment with either DMI or iprindole tended to decrease brain and plasma tyrosine.