The association between the onset of depressive illness and the paramenstruum has been reported. In the present study, we looked at changes in platelet 5-HT uptake in six healthy, regularly menstruating subjects on days 1, 10, and 24 of three consecutive menstrual cycles to explore possible biochemical bases for mood changes associated with menstruation. Platelet 5-hydroxytryptamine (5-HT) uptake was determined by suspension of platelet pellets in 0.5-5 microM hydroxy [G-3H] tryptamine [( 3H]-5-HT) creatinine sulfate solution at 37 degrees C and measurement of radioactivity of [3H]-5-HT in the platelets using liquid scintillation counting. Mood changes were measured using the Moos Menstruation Distress Questionnaire and the Spielberger State Anxiety Scale. Analysis of variance and trend analysis revealed significant elevation of Km and Vmax on day 24 of the cycle, which was consistent across the three menstrual cycles studied. A significant linear rise of "negative affect" across each cycle peaking on day 1 was detected. "Water retention" and "behavioral change" also peaked on day 1. No significant correlation, however, was obtained between the mood scores and platelet 5-HT uptake. These findings are discussed.