Growth hormone-releasing hormone (GHRH) has been shown to enhance slow-wave sleep (SWS) and non-rapid eye movement sleep in animals and humans. In animals the somnogenic effect of interleukin (IL)-1β appears to be mediated by GHRH. Neuroimmunological interactions in sleep are most frequently studied in humans by sleep deprivation or by cytokine administration. The present study, in contrast, investigates in humans the effect of enhanced sleep through GHRH administration on selected immune parameters. Results reveal that a single intravenous bolus of 50 μg GHRH which enhanced SWS stage 4 in the first half of the night suppressed circulating suppressor T cell (CD3+/CD8+) numbers, with a similar tendency for B cells (CD19+) and suppressed mitogen-stimulated IL-β production. When the same amount of GHRH was administered distributed across five repetitive boluses of 10 μg GHRH within 1 h, neither corresponding sleep nor immune parameters were changed significantly compared to placebo. These data suggest that GHRH can modulate immune functions through brain mechanisms which are also involved in the regulation of sleep.