We studied the effect of 3 weeks of moderate calorie restriction on 5-HT-mediated prolactin (PRL) release in healthy volunteers using the 5-HT-releasing agent d-fenfluramine. In women, dieting significantly lowered plasma total and free tryptophan (TRP) and increased the PRL response to d-fenfluramine. None of these measures were altered in men who dieted. These findings add to the data indicating that dieting alters brain 5-HT function in women, perhaps as a consequence of reducing the availability of plasma TRP.