In fish, the hypothalamus-pituitary-interrenal axis (HPI-axis), the equivalent of the hypothalamus-pituitary-adrenal axis (HPA-axis) in mammals, is activated during stress and leads to production and release of cortisol by the interregnal cells in the head kidney. In mammals, the cytokine interleukin-1beta (IL-1beta) takes a key position in the innate immune and inflammatory responses and influences the HPA-axis. In fish, studies that address the effects of cytokines on HPI-axis activation are limited. We quantitatively assessed expression of IL-1beta and its receptor, IL-1RI (the latter was cloned and sequenced), in an acute restraint stress paradigm in common carp, Cyprinus carpio. We also considered expression of the pituitary hormones prolactin (PRL) and GH that have been shown to be structurally related to cytokines and have immunomodulatory actions. Pituitary PRL expression increased fourfold during stress; GH mRNA levels were unaffected. Following restraint, hypothalamic IL-1beta expression was upregulated; in head kidney and pituitary pars intermedia, IL-1RI expression significantly increased. We suggest that during acute stress IL-1beta signalling in the HPI-axis becomes more sensitive, since both ligand and receptor expressions are enhanced. In vitro, recombinant carp IL-1beta stimulates release of alpha-MSH and N-Ac beta-endorphin from the pituitary gland. This observation concurs with increased in vivo plasma levels of alpha-MSH and N-Ac beta-endorphin following restraint. Our findings combined lead us to conclude that IL-1beta affects the activity of the HPI-axis and, in turn, expression profiles of genes encoding IL-1beta and its receptor are modified during acute stress. Our study provides convincing evidence for bi-directional communication of the HPI-axis and the immune system in fish.