In a randomized controlled clinical trial, 37 patients with premenstrual dysphoric disorder were treated with L-tryptophan 6 g per day and 34 were given placebo. The treatments were given under double-blind conditions for 17 days, from the time of ovulation to the third day of menstruation, during three consecutive cycles. Visual Analog Mood Scales revealed a significant (p = 0.004) therapeutic effect of L-tryptophan relative to placebo for the cluster of mood symptoms comprising the items dysphoria, mood swings, tension and irritability. These results suggest that increasing serotonin synthesis during the late luteal phase of the menstrual cycle is therapeutic in patients with premenstrual dysphoric disorder.