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Immune function (mitogen and antigen stimulation, suppressor cell activity, T-cell subpopulation distribution) and immunogenetics (HLA-gene determination) were studied in 13 patients with histiocytosis-X and in 88 healthy controls. We found three clusters with significantly different immune responses (F-values greater than 4-20, p less than 0.05-0.001) against mitogenic and antigenic stimulation among the controls which differed, too, in HLA-gene distribution. As suppressor cell activity and T-cell subpopulation distribution are the same in all three control clusters, these reactivity differences should be functional ones and may be genetically determined. Patients with histiocytosis-X show a significantly reduced suppressor cell activity and their helper cells are significantly reduced compared to the controls (p less than 0.01). Furthermore, their lymphocyte reactivity does not correspond with their immunogenetics, but is significantly reduced (p less than 0.05-0.001). Suppressor cell activity, helper cells and lymphocyte reactivity normalized in all eight patients treated systemically with thymostimulin (Tp-1 Serono). It seems to be possible therefore, to influence immunological aberrations in vivo by thymostimulin. In our opinion, the results of this study justify further investigations of the immunoregulatory mechanisms of histiocytosis-X and larger prospective clinical trials with thymic factors to find out, whether such a therapy may be a real alternative to the conventional therapeutic approach in this disease.