We have previously demonstrated that the chronic inflammatory stress of adjuvant-induced arthritis in rats can alter levels of the neuropeptides adrenocorticotropin (ACTH), β-endorphin, arginine vasopressin (AVP) and corticotropin-releasing hormone (CRH) in tissues of the immune system. We now present data showing that the patterns of these changes in the spleens and thymuses of Piebald-Viral-Glaxo rats are quite dissimilar throughout the course of the disease. Immunoreactive (ir)-CRH, AVP, ACTH and β-endorphin were measured by radioimmunoassays in spleen and thymic extracts taken at days 3, 7, 11 and 14 following injection of adjuvant. AVP was increased in the spleen at day 14 compared to the controls (79.4 ± 4.4 and 60.0 ± 9.0 fmol/g tissue respectively), but no change occurred in the thymus. CRH contents were increased in the spleen at day 14 (33.4 ± 3.5) compared to controls (22.1 ±2.4 fmol/g tissue), and in the thymus at day 11 (24.0 ±2.3) compared to controls (14.1 ± 2.5 fmol/g tissue). Increases in ACTH content were observed in spleens from arthritic rats at days 3 (365 ± 23), 11 (359 ± 32) and 14 (355 ± 45 fmol/g tissue) compared to controls (198 ± 37 fmol/g tissue). In the thymus, however, ACTH was elevated only at day 14. β-Endorphin levels in the spleen were elevated only at day 14 (289 ± 41) compared to controls (97 ± 22 fmol/g tissue). We conclude that the responses of ir-CRH, AVP, ACTH and β-endorphin to an inflammatory stress in the spleen and thymus are activated at different time-points and by different events which occur during the course of a chronic stress. It is also apparent, at least in the spleen, that unlike the hypothalamo-pituitary axis, immune POMC activation is not necessarily consequent to increases in immune CRH or AVP.