In recent years, it has been demonstrated that neuroendocrine and immune systems are functionally correlated. In particular, hypothalamic-pituitary-adrenal axis may be activated by a cytokine, interleukin- 1 which stimulates corticotropin releasing hormone (Sapolsky, Rivier, Yamamoto, Plotsky & Vale, 1987) and eventually determines an increase in corticosteroids which, in turn, inhibit interleukin- 1 production (Besedovsky, Del Rey, Sorkin & Dinarello, 1986). This immune-endocrine feedback loop may be a relevant mechanism of control of the immune response and it has been suggested that an impairment of this circuit may be involved in certain autoimmune disease (Schauenstein, Fassler, Dietrich, Schwarz, Kromer & Wick, 1987). Information about endocrine-immune connections in human subjects derived from in vivo studies is very scanty. A report by Meyer, Smith, Richards, Cavallo, Morril, and Blalock (1 987) investigating cortisol response to typhoid antigen in hypopituitary children, demonstrated that immunization elicits a significant increase in cortisol secretion in normal subjects and no response in hypopituitary children. The aim of this paper was to investigate the adrenal response to antigenic challenge in normal adult subjects. 15 normal subjects, 9 men and 6 women, aged 23-52yr were included in this study. All had received a primary immunization series. After giving informed consent, each subject received either 0.5 ml of saline or tetanic toxoid (Anatetall, Sclavo) intramuscularly at 09:OO hr in two nonconsecutive days. Blood samples were collected from an indwelling heparinized catheter at 0, 1, 2, 4, 6, 8, and 10hr after injection. Plasma specimens were analyzed by radioimmunoassay techniques for ACTH, prolactin (PRL), growth hormone (GH), and cortisol levels using commercially available kits. Results were assessed for statistical significance by means of the paired t test. During control test, cortisol levels decreased regularly in serial sampling. After antigenic challenge, cortisol concentrations at 4 and 6 hr were significantly higher than those observed at the same intervals of the control test (mean f SEM; 12.50pg/ dl +_ 0.87 vs 9.37 +_ 0.66 at 4hr; p = .01; and 9.73 k .62 vs 7.77 +_ .55 at 6hr, p = .02, respectively)(Figure 1). At baseline, plasma ACTH, GH and PRL levels were in normal range and showed minor fluctuations following either saline or tetanic toxoid injection in all subjects. Our data demonstrated that an antigenic stimulation determined a significant rise