OBJECTIVE To investigate muscarinic cholinergic receptors on lymphocytes from various subsets of patients with rheumatoid arthritis (RA). METHODS The level of muscarinic receptors on peripheral blood lymphocytes from 38 patients with various subsets of RA [5 with inactive, 13 with active RA, 13 with rheumatoid vasculitis and 5 with reactive secondary amyloidosis (RSA)] was determined by the binding studies of specific muscarinic ligand [3H] quinuclidinyl benzilate in comparison to healthy individuals. RESULTS Expression of muscarinic cholinergic receptors on lymphocytes in patients with RA was significantly higher (mean 1022; SD +/- 567) compared to healthy individuals (mean 647; SD +/- 170) (p < 0.01). The phytohemagglutinin (PHA) stimulation index in acetylcholine treated lymphocytes in patients was statistically significantly lower than in healthy individuals (p < 0.05). The highest levels of muscarinic receptors on lymphocytes was observed in patients with RA with vasculitis and RSA and showed a significant correlation with disease activity. The number of muscarinic receptors on lymphocytes as well as PHA stimulation index in acetylcholine treated and untreated lymphocytes showed a tendency to decrease after the treatment. The number of muscarinic receptors on lymphocytes decreased significantly after the treatment only in the group of patients with clinical improvement (p < 0.05). CONCLUSIONS Our results suggest that cholinergic stimulation may be connected with activity and/or heterogeneity of the disease in patients with RA.