Interferon-alpha (IFN-alpha) therapy for hepatitis and malignant tumor frequently results in autoimmune thyroid disease (AITD); this fact indicates an association of IFN-alpha with autoimmunity. In order to study the mechanism, an investigation of the effects of human IFN-alpha on T cells, T cell subpopulations, B cells, macrophages and natural killer cells of patients with AITD and normal controls was carried out. It has been found that T cells were inhibited by IFN-alpha with dosage dependency, particularly the T suppressor (CD8/CD11b) in both the patients with AITD and normal controls. An increase in number of B cells and macrophages with stimulation of IFN-alpha was also found in both groups. The results suggest that the decrease of suppressive T cells and increase B cells and macrophages may be responsible for IFN-alpha induced autoimmunity.