Rheumatoid arthritis (RA) is a systemic inflammatory disease with elevated levels of proinflammatory cytokines in peripheral blood, especially IL-6, but also IL-1 alpha and TNF alpha, for example, in different concentrations, depending on disease activity. A disturbed circadian rhythm of cortisol secretion and an overall elevated cortisol release in active RA, depending on disease activity, is known. The presented study examined correlations of IL-6 as the most important systemic mediator of the acute phase response in active RA with classical humoral disease activity parameters, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and with serum cortisol. We investigated 64 active RA patients, previously untreated with glucocorticoids. IL-6 was measured by ELISA from Pharmingen (San Diego), ESR by the method of Westergren and CRP by nephelometry (Behring Marburg, Germany). Cortisol was measured in 34 of these patients, using a fluorescence-polarization immunoassay (FPIA) from Abbott. We found correlations of IL-6 with CRP (p < 0.001, Spearman Rank Test, rs = 0.75), with ESR (p < 0.001, rs = 0.62) and with serum cortisol (p = 0.019, rs = 0.401). ESR and CRP correlate (p < 0.001, rs = 0.8) and cortisol also correlates with ESR (p = 0.002, rs = 0.52) and CRP (p < 0.001, rs = 0.57). IL-6 as an important systemic mediator of inflammation in RA correlates closely with CRP, as it induces its production, and with ESR. These three parameters correlate well with serum cortisol, which is increased in active RA, depending on disease activity. Thus, IL-6 is an important disease activity parameter in RA that is closely related to both the classical humoral disease activity and the HPA axis.