Various evidence suggests a bidirectional circuit between the immune and neuroendocrine systems. Because of the well-known role of the thymus in the regulation of the immune function, we designed this study to determine whether the lack of thymus may affect hypothalamo-pituitary-adrenal (HPA) axis activity by using both in vivo and in vitro paradigms in Swiss nude (athymic) and BALB/c (normal) mice. Eight-week-old female mice of both strains were used to study: (a) the in vivo response of the HPA axis to various stress stimuli acting at either hypothalamic (ether vapor inhalation, insulin administration), pituitary (CRH injection) or adrenal (ACTH treatment) level and (b) the in vitro response of pituitary and adrenal cells to CRH and ACTH stimulation, respectively. The results indicate that: (1) basal plasma ACTH levels were significantly (p < 0.05) higher in Swiss nude than in BALB/c mice, whereas basal plasma corticosterone (B) concentrations were similar in both strains of mice; (2) the stress-induced release of ACTH and B in plasma were significantly (p < 0.05) lower in Swiss nude than in BALB/c mice, regardless of the stimulus applied; (3) the in vitro pituitary response to CRH and the adrenal response to ACTH were significantly (p < 0.05) lower in Swiss nude than in BALB/c mice, whereas (4) hypothalamic CRH and pituitary ACTH contents were similar in both strains, adrenal B concentration was significantly (p < 0.05) lower in athymic mice; in addition, the nude mice adrenal glands were larger than those of BALB/c animals, due to marked hypertrophy of the zona fasciculata.(ABSTRACT TRUNCATED AT 250 WORDS)