In order to study the genetic factors involved in the neuroendocrine responses to stress, we have compared the intensity of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system activation following a 60 minute-restraint stress or after a 10 minute-exposure to a novel environment in three rat strains : outbred Wistar, inbred Brown Norway and Fischer 344, and F1 hybrid Brown Norway x Fischer 344 rats. The basal activity of the HPA axis did not differ between the four groups of rats whereas Brown Norway rats had the lowest release of corticosterone following restraint stress. Although differences in plasma adrenocorticotropic hormone failed to reach significance after exposure to a novel environment, the lowest level of corticosterone was found in Brown Norway rats. This lower release of corticosterone in Brown Norway rats has probably an adrenal origin as suggested by the ratios of corticosterone to ACTH levels following exposure to a novel environment: 632 +/- 222, 200 +/- 45, 636 +/- 89, 258 +/- 65 in Wistar, Brown Norway, Fischer 344 and F1 hybrids, respectively. This trait was dominant over the "adrenal responsive" phenotype of the Fischer 344 rat strain. In response to novelty, the lowest levels of prolactin and renin activity were found in plasma of Brown Norway and Wistar rats and the highest in Fischer 344 and F1 hybrid Brown Norway x Fischer 344 rats, the "high response" phenotype of the Fischer 344 strain being dominant. No strain-related difference was found in plasma glucose and either adrenal tyrosine hydroxylase or phenylethanolamine N-methyl transferase activity. Taken together, these data suggest that 1) genetic factors might contribute to the interindividual differences in neuroendocrine responses to stress and 2) subsets of these responses are controlled by specific genetic factors.