There is growing evidence that the autonomic nervous system influences the immune response by activation and modulation of beta 2-adrenergic receptors (beta 2R) on immunocompetent cells. However, little is known about its pathogenetic role in autoimmune disease. Therefore, the number and the dissociation constants (beta 2R-KKD) of beta 2R on peripheral blood mononuclear cells (PBMNC) were determined in 21 patients with rheumatoid arthritis (RA) and 9 healthy age and sex matched controls [healthy donors (HD)] by a radioligand binding assay with [125I]iodocyanopindolol. The density of beta 2R (x +/- SEM = 2,120 +/- 103 binding sites/cell) and the beta 2R-KD (x +/- SEM = 6.8 +/- 0.8 pM) were significantly decreased in patients with RA compared to HD (number of beta 2R: 3,960 +/- 372, beta 2R-KD: 16.7 +/- 3.6, p less than 0.01). In RA, the number of beta 2R was significantly lower in patients with high systemic disease activity (n = 11, number of beta 2R: 1,850 +/- 134) than in patients with low inflammatory activity (n = 10, number of beta 2R: 2,418 +/- 95, p less than 0.004). In addition, there were significant negative correlations between the beta 2R density and an arbitrary systemic activity score (r = -0.74, p less than 0.001), the Ritchie index (r = 0.77, p less than 0.001), and various variables of disease activity (r = 0.59 to -0.78, p less than 0.005), respectively. Our data demonstrate the close interplay between the systemic inflammatory activity and the beta 2R characteristics in patients with RA. Our results provide further evidence that the immune response may be influenced by the sympathetic nervous system.