The objective was to evaluate the expression of the multidrug resistance P-glycoprotein (P-gp) in peripheral blood lymphocytes (PBL) of patients with rheumatoid arthritis (RA). PBL from 68 RA patients and 44 controls were evaluated. RA patients had a mean disease duration of 10.7 yr, with a mean number of past resistances to DMARDs of 0.82, and were treated with NSAIDs (n = 34), DMARDs (n = 25) and prednisolone (n = 40). Fluorescence flow cytometry was used to assess P-gp membrane expression on PBL. In the RA group, the percentage of PBL expressing P-gp was higher in patients treated with prednisolone than in other patients [mean +/- S.D.: 10.7 +/- 15.8% vs 3.3 +/- 7.6%, P < 0.03, Student] and was not related to other therapies, age, sex, RA duration, number of past resistances to DMARDs, activity, ESR, CRP. The percentage of PBL expressing P-gp did not differ in RA and control groups, but was higher in the prednisolone-treated RA patients than in controls. Prednisolone could induce a rise in the percentage of PBL expressing P-gp. On the contrary, patients with a high percentage of PBL expressing P-gp could be more resistant to DMARDs and need prednisolone earlier. Further studies are needed to address this question and to evaluate the potential implication of P-gp in drug resistance in RA.