The purpose of this work was to compare the plasma adrenocorticotropin (ACTH), corticosterone and interleukin-6 (IL-6) responses that rats of the outbred Sprague-Dawley strain obtained from two different vendors: Charles River (CR) and Harlan (HSD). Basal plasma ACTH and IL-6 concentrations were similar in rats from either vendor (HSD or CR), while CR animals exhibited slightly elevated corticosterone levels in late afternoon. Inflammatory stimuli such as lipopolysaccharide (LPS) (1 µg/kg, i.v.) or turpentine (50 µl/100 g, i.m.) which induce the production of endogenous cytokines, produced a significantly larger ACTH response in CR, compared to HSD rats, while the overall corticosterone responses were comparable in both rat groups. This could probably not be accounted for by a greater ACTH responsiveness in CR rats per se because CR and HSD rats showed similar peak ACTH responses to electrofootshock. Furthermore, in contrast to when the stimulus was one that induced endogenous cytokine production, the administration of exogenous interleukin-1β (IL-1β, 200 ng/kg, i.v.) produced a 2-fold greater rise in plasma ACTH concentrations in HSD rats compared to CR rats. The plasma IL-6 responses to the inflammatory stimuli showed a similar pattern to ACTH, with LPS and turpentine tending to pruduce greater IL-6 responses in CR rats, though these differences were not statistically significant. In contrast HSD rats had a significantly greater IL-6 response to IL-1β than did CR rats. Collectively, these results show that Sprague-Dawley rats obtained from different commercial sources can differ in immune-neuroendocrine responses to inflammatory stimuli.