Prostaglandin (PG) E2 is produced by mammalian hypothalamus and when administered exogenously prolongs wakefulness. In order to study the relation of endogenous hypothalamic PGE2 to sleep and wakefulness, we have used microdialysis in freely moving rats associated with EEG recording. Male Wistar rats were implanted with three cortical electrodes and with a guide cannula for microdialysis in the space between the paraventricular nucleus (PVN) and the ventromedial hypothalamus (VMH). PGE2 was measured by RIA in 3- or 6-min dialysates 15 days after surgery, when sleep patterns were normal again and PGE2 production stabilised. PGE2 levels were significantly higher during wakefulness (601 +/- 35 pg/ml, 5 experiments, 35 samples) than during slow-wave sleep (487 +/- 24 pg/ml, 5 experiments, 49 samples). Samples corresponding to paradoxical sleep showed a tendency towards higher PGE2 values compared to slow-wave sleep but lower compared to wakefulness. In epochs of wakefulness or sleep lasting at least 12 min, high PGE2 levels in the middle of wakefulness regularly dropped, thus announcing the occurrence of sleep. During sleep, PGE2 first went on dropping and then reincreased towards the values that characterize early periods of wakefulness. In its turn, this reincrease in PGE2 announced the end of sleep and the imminent occurrence of wakefulness. It is the first study to our knowledge showing that the evolvement in endogenous PG profile may predict the occurrence of sleep or wakefulness.