Twenty selected patients suffering from severe, long-standing rhumatoid arthritis (RA) not controlled by anti-inflammatory drugs (19 cases) and from disseminated lupus erythematosis (DLE) (1 case) were treated with levamisole. The subjects were divided into 2 groups: Group I comprised fourteen patients (13 RA and 1 DLE) treated continuously by levamisole 150 mg/day for 3 or 6 months then on an intermittent regime (150 mg/day-3 days per week). Group II comprised 6 RA patients treated on the intermittent regime from the beginning. In Group I, following average treatment of 9 months (5-12 months), clinical results assessed according to precise clinical criteria were favorable in 9 out of eleven cases. In the other 2 cases no change was noted. Side effects included reversible agranulocytosis in 9 cases, on 3 occasions this necessitated the discontinuation of treatment. A signifcant reduction in sedimentation rate was noticed in 5 cases out of eleven and in 3 patients the Rose-Waller test turned negative. A monoclonal disglobulinemia of IgG lambda appeared under treatment in 1 patient who was deficient in IgA. Skin tests carried out periodically showed a significant augmentation of the response to candida. Lymphocyte culture in the presence of mitogens gave highly variable results from one control to the other in the same subject, as well as in the treated subjects as in the group of RA not receiving levamisole. These results are compared with those previously published; the mechanism of action and possible indications for levamisole in RA are discussed.