Agranulocytosis, which must be differentiated from leukopenia, was seen as the most severe side effect of levamisole in the treatment of rheumatoid arthritis (RA). By sending a detailed questionnaire to each investigator known to have been confronted with leukotoxic side effects, data were collected on 88 patients with agranulocytosis, 43 patients with leukopenia and three with thrombocytopenia. The presence of HLA B27 in seropositive RA patients was found to be an important predisposing factor for agranulocytosis. This blood dyscrasia caused by levamisole was similar to the agranulocytosis found with other antirheumatic and anti-inflammatory drugs and could be classified as agranulocytosis of the immunological type. In this form no bone marrow toxicity occurred and the agranulocytosis was always spontaneously reversible on discontinuation of the drug. Although the incidence of agranulocytosis did not seem to be reduced by any of the treatment schemes, high risk patients could be detected by the single day per week regimen. Treatment with 150 mg levamisole on one day per week, with leukocyte count 10 hours after each intake of the drug, undoubtedly appeared to be the most efficient way to prevent agranulocytosis and makes this drug safe in the treatment of RA.