The catecholamine hypothesis of affective disorders postulates that depression reflects inadequate norepinephrine activity at unspecified brain centers that regulate mood. In light of experimental data showing that the oral administration of tyrosine, precursor of the catecholamine series of neurotransmitters, can increase brain norepinephrine concentrations and activity, we have conducted preliminary trials of tyrosine in depressed outpatients. Initial results are encouraging, and we are now conducting a double-blind, parallel-group trial comparing tyrosine to the tricyclic antidepressant imipramine and to placebo in non-bipolar outpatients with major depression.