The diurnal rhythm of platelet serotonin (5-HT) content and plasma alpha-1-acid glycoprotein (AGP) was investigated in twelve healthy male volunteers aged 19-30 years. Platelet 5-HT content and plasma AGP concentration varied across a twenty-four hour sampling period in a manner consistent with a circadian pattern. Platelet 5-HT levels rose from baseline at 5.00 hr to a peak at 14.00 hr and slowly declined to baseline during the night-time hours. A concordant pattern was observed for plasma AGP with peak concentrations occurring between 8.00 hr and 14.00 hr. These findings support the notion that AGP is a positive endogenous allosteric stimulator of platelet 5-HT transport, since there is a direct relationship between platelet 5-HT levels and plasma AGP concentration. A theoretical model is presented to explain the diurnal effects of AGP on the platelet 5-HT transporter.