Interleukin-1 beta stimulates oxytocin and vasopressin release in conscious, male rats and causes a rise in blood pressure. These experiments were done to : A) examine the effect of i.c.v. interleukin-1 beta (1 ng/microliter) on circulating levels of vasopressin in female rats at different stages of lactation and B) determine if alpha-adrenergic mechanisms and/or prostaglandins were involved as mediators. Urethane-anaesthetized nonlactating rats and rats at Day 7, 10, 20 and 26 of lactation were set up for arterial blood sampling and i.c.v. injections. One mL blood samples were obtained in one min periods before, and at 1, 2.5, 5, 10, 30, 60 and 120 min after the following treatments: i.c.v. treatment with either interleukin-1 beta (1 ng in 1 microliter PBS-BSA) or PBS-BSA (1 microliter) as a vehicle control; or i.c.v. treatment with interleukin-1 beta following pretreatment with either phentolamine (1.7 micrograms/microliter i.c.v.) or indomethacin (1 microgram/microliter i.c.v.). As blood was sampled, isotonic saline was infused (1 mL per min) and blood pressure was monitored to minimize any hypovolemic effects due to sampling. Extracted plasma was assayed using a specific vasopressin radioimmunoassay. Interleukin-1 beta i.c.v. stimulated the release of vasopressin above that elicited by PBS-BSA alone in non-lactating rats resulting in an approximate 1.2 to 2-fold increase in plasma hormone levels. Throughout the first half of lactation, vasopressin responsiveness to i.c.v. interleukin-1 beta treatment was markedly attenuated. In latter stages of lactation, the response recovered and resembled that of non-lactators around the time of weaning. Prostaglandins consistently mediate a stimulatory action of interleukin-1 beta on vasopressin release whereas alpha-adrenergic mechanisms mediate a depression of interleukin-1 beta-induced vasopressin release during the early to middle stages of lactation. It is possible that the depression in interleukin-1 beta-stimulation of vasopressin release in early to mid-lactation is conducive for nursing to occur and that the increase in vasopressin responsiveness towards the latter stages of lactation represents a component of the weaning process.