Catecholamines have been implicated in the etiology and pathophysiology of mood and anxiety disorders. In the present study, we investigated the effects of experimentally reducing catecholamine neurotransmission by means of acute phenylalanine/tyrosine depletion (APTD). Healthy female volunteers ingested: (1) a nutritionally balanced amino acid (AA) mixture (n = 14); (2) a mixture deficient in the serotonin precursor, tryptophan (n = 15); or (3) one deficient in the catecholamine precursors, phenylalanine and tyrosine (n = 12). Mood was measured at three times: at baseline and both immediately before and after an aversive psychological challenge (public speaking and mental arithmetic) conducted 5 hours after AA mixture ingestion. Acute tryptophan depletion (ATD) lowered mood and energy and increased irritability scores. These effects were statistically significant only after the psychological challenge. The effect of APTD on mood was similar to that of ATD. APTD did not attenuate the anxiety caused by the psychological challenge. These findings suggest that, in healthy women, reduced serotonin and/or catecholamine neurotransmission increases vulnerability to lowered mood, especially following exposure to aversive psychological events.