The effects of intracerebroventricular (icv) administration of porcine corticotropin-releasing hormone (pCRH) and cortisol on the immune system and behavior were examined in domestic pigs. In Experiment 1, 50 micrograms of pCRH in 200 microliters of saline or 200 microliters of vehicle was administered i.c.v. at 0600 h. Blood samples were obtained at 0600 (prior to injection), 0700, and 0800 h. Plasma cortisol concentrations were higher at 1 and 2 h after pCRH than after saline. Generally, pCRH failed to effect NK cytotoxicity or lymphocyte proliferation in response to phytohemagluttin (PHA). However, 1 h postinjection, pigs administered pCRH i.c.v. had marginally lower NK activity than control pigs. Pigs injected with pCRH had substantially lower neutrophil chemotaxis (CHTX) than the control pigs at 1 and 2 h postinjection. As blood cortisol concentration increased, neutrophil CHTX decreased. Pigs injected i.c.v. with pCRH had higher neutrophil numbers and neutrophil:lymphocyte ratios than control pigs. Percentage of lymphocytes was higher among control than treated pigs. Central pCRH increased overall activity, particularly walking, standing, licking, rooting, and increased activity-related sequences (e.g., sit, walk and stand, walk), but reduced complex oral/nasal sequences (e.g., root, lick). In Experiment 2, pigs were injected i.c.v. with 10 micrograms of cortisol in 200 microliters of saline or with vehicle at 0600 h. Administration of cortisol failed to effect NK cytotoxicity, lymphocyte proliferation, CHTX, or leukocyte distribution. Pigs given cortisol had no apparent change in behavior. These data indicate leukocyte distribution and specific neutrophil function in pigs were significantly modulated by stress-related hormones of the hypothalamic-pituitary-adrenal axis and complexity of behavioral sequences (pigs repeating certain behavioral sequences) associated with increased activity was reduced. Oral/nasal stereotypies (as seen among confined sows) were not elevated among pigs given i.c.v. pCRH. CRH given by i.c.v. administration may serve as a better model for acute rather than chronic stress.