It has been observed that patients with rheumatoid arthritis (RA) respond differently to repetitive painful stimulation. The present study investigated whether this is related to the peripheral or central nervous nociceptive system. EEG-derived potentials and the negative mucosal potential (NMP) from the respiratory epithelium were recorded in response to painful intranasal stimulation with gaseous CO2. Differences between groups (12 RA patients, 12 controls) were found when stimuli were presented at short intervals. While the NMP did not differ between groups, patients had larger cortical responses to the first stimuli of a series of painful stimuli. This may indicate that in RA central nervous changes of nociceptive processing are present. (C) 2000 Elsevier Science B.V. All rights reserved.