To investigate whether autoimmune thyroiditis [HT] (i.e., a TH1 disease) influences the pattern of peripheral lymphocyte activation in systemic sclerosis [SSc] (commonly regarded as a TH2 disease). Twenty SSc patients, 6 with (SSc+HT+) and 14 without HT (SSc+HT-) and 20 controls were investigated for the intracellular content of IFN-gamma and IL-4 in unstimulated and stimulated (25 ng/ml PMA and 1 microg/ml ionomycin) CD4+ and CD8+ T lymphocytes. Results Under basal conditions the percentages of CD4+IFN-gamma, CD4+IL-4+ and CD8+IFN-gammawere significantly higher in the patients than the control subjects, no significant differences being detectable between the two patient subgroups. Upon PMA stimulation, the 20 SSc patients showed a higher percentage of CD4+IFN-gamma+ and CD8+IFN-gamma+ than the control subjects. In particular, the 14 SSc+HT- patients showed a higher number of CD4+IFN-y+ and CD4+IL-4+ cells, while the SSc+HT+ patients showed higher percentage of CD8+IFN-gamma+ cells. The latter patients showed a reduced percentage of CD4+IL-4+ cells and an increased percentage of CD8+IFN-y+ in comparison with the SSc+HT- patients. Type-1 activation in the peripheral blood of SSc patients has been already pointed out by other authors and ourselves. This study shows that such activation mainly affects SSc patients with coexistent HT.