The aim of this study was to investigate imidazoline(2) (I(2)) binding site- and alpha(2)-adrenoceptor-mediated control of central noradrenergic and HPA axis activity in control rats and chronically stressed rats with adjuvant-induced arthritis (AA). Basal levels of extracellular nonadrenaline (NA) in the region of the hypothalamic paraventricular nucleus (PVN) of AA rats were significantly greater than controls. Both the I(2) binding site selective ligand BU224 (10 mg kg(-1) i.p.) and the alpha(2)-adrenoceptor antagonist RX821002 (2.5 mg kg(-1) i.p.) significantly elevated extracellular levels of NA in the PVN region and plasma corticosterone (CORT) in a rapid and transient manner in both control and AA rats. The noradrenergic response of AA rats to BU224 was significantly enhanced compared with drug treated controls. There was a significant correlation between extracellular NA in the PVN region and plasma CORT following BU224 and RX821002. In conclusion, central noradrenergic and HPA axis activity in control and chronically stressed AA rats appear to be under the control of both I(2) binding sites and alpha(2)-adrenoceptors. Increased basal levels of extracellular NA in the PVN region of AA rats suggests increased noradrenergic activity in these animals which is modulated to a greater extent by I(2) binding sites than by alpha(2)-adrenoceptors.