OBJECTIVE To study the dynamic response of the hypothalamo-pituitary- adrenal axis and of prolactin (PRL) pituitary secretion in rheumatoid arthritis (RA). METHODS We performed a cortisol releasing hormone (CRH) provocation test followed by determination of adrenocorticotropin hormone (ACTH), beta-endorphin, and cortisol concentration, and then a thyrotropin releasing hormone (TRH) provocation test followed by assessment of PRL pituitary secretion in 10 patients with RA and 5 control subjects. All were women under 40 years of age. Hormone concentrations were assessed by radioimmunoassay. RESULTS Basal PRL cortisol, and ACTH concentrations were similar in patients with RA and controls. We observed a dissociation between the pituitary secretion of beta-endorphin and of ACTH in response to CRH in RA. The ACTH peak and total ACTH production (area under the curve, AUC) were similar in the 2 groups. In contrast, basal beta-endorphin was increased in RA (12.6 +/- 1.41 vs 8.29 +/- 0.144 pg/ml), and the response upregulated (AUC: 83,080 +/- 12,000 vs 54,200 +/- 2400) after CRH compared to controls (p < 0.05). Cortisol adrenal response curve was blunted, but did not reach statistical significance. In contrast, the PRL response to TRH was increased at 120 and 150 min (3461 +/- 303 vs 1897 +/- 520 muIU/ml)(p < 0.01) in patients with RA, independent of disease activity. CONCLUSIONS We observed upregulated pituitary PRL secretion in RA, and a dissociation of ACTH stress. The implication concerning the neuroendocrine system in the chronic immune response in RA is discussed.