OBJECTIVE Agranulocytosis is a serious side effect of anti-thyroid drugs (ATD), Granulocyte colony-stimulating factor (G-CSF) is one of the cytokines that increase granulocyte number. The aim of this study was to examine the sequential variation of serum G-CSF levels in patients with Graves' disease before and after ATD therapy, PATIENTS Sixty-three patients with Graves' disease were studied before, during and after treatment with methimazole (MMI). Serum samples from 71 healthy subjects were used as controls, DESIGN AND MEASUREMENTS Serum levels of G-CSF were measured by a never chemiluminescent enzyme immunoassay, which was sensitive enough to determine G-CSF levels in healthy subjects, Blood granulocyte counts, serum, thyroid hormone and TSH levels, and titres of thyroid autoantibodies were also measured, RESULTS Serum G-CSF levels in Graves' patients before and 2 weeks after MMI were significantly higher than in healthy subjects, There was a significant correlation between serum G-CSF levels and granulocyte counts in untreated patients with Graves' disease. Untreated patients with granulocyte counts less than 2x10(9)/l had significantly lower serum G-CSF levels as compared with other untreated patients, Serum G-CSF levels gradually decreased thereafter. No correlation was observed between serum G-CSF levels and serum thyroid hormone levels or titres of thyroid autoantibodies. After ATD treatment, no correlation was found between serum G-CSF levels and granulocytes counts. There was no significant correlation between the change of serum G-CSF levels and that of granulocyte counts before and after MMI treatment. Graves' patients with mild agranulocytosis had normal or elevated serum G-CSF levels, CONCLUSIONS Significantly elevated serum G-CSF levels were observed in patients with Graves' hyperthyroidism. During ATD therapy, deficiency of G-CSF was not identified as a cause of agranulocytosis in this study.