Ether-laparotomy stress resulted in a dramatic decrease in specific iodine-125-labeled ovine CRF binding ([125I]oCRF) in the pituitary at 6 h after the onset of the stress although it did not affect [125I]oCRF binding in the pituitary at 2 h after the stress. [125I]oCRF binding was unchanged in the frontal cortex after the stress. In contrast, [125I]interleukin-1 (IL-1)alpha binding was significantly increased in the pituitary at 2 h after the stress and tended to be higher than non-stressed levels at 6 h after the stress but was not statistically significant. Ether-laparotomy stress did not affect [125I]IL-1 alpha binding in hippocampus, spleen and testis at any time after the stress. Plasma adrenocorticotropic hormone (ACTH) and corticosterone were increased at 2 h after the stress. These data demonstrate complex interactions between CRF and IL-1 receptors on HPA axis during stress.