OBJECTIVE To investigate whether high-frequency periodic fluctuation in the release of plasma immunoreactive (ir)-beta-endorphin occurs in humans. DESIGN, PATIENTS AND MEASUREMENTS Blood was collected at 90-sec intervals for 1 hour from the forearm vein of four healthy women and subsequently analysed for ir-beta-endorphin by radioimmunoassay. RESULTS In all women circulating beta-endorphin release followed a high-frequency periodic rhythm pattern. The estimated spectral densities within the four subjects varied between 3.6 min to 4.9 min. CONCLUSIONS Our results provide the first in vivo evidence that fluctuations in the release of beta-endorphin in humans cannot only be characterized by low-frequency pulses, but also by a high frequency periodic rhythm.