Thirty-one patients with PSS (scleroderma) were examined for evidence of abnormalities in T lymphocyte subsets. TG and TM subpopulations of peripheral blood T lymphocytes were enumerated by rosetting techniques. The helper-suppressor functions of these lymphocytes were studied in the PWM-activated in vitro assay. The absolute numbers of TG cells in patients with DS as well as those with the CREST syndrome variant of PSS were decreased in comparison with those in age-matched healthy controls (p < 0.05). The numbers of TM and T "null" cells were not significantly altered (p > 0.05). The reduction in the number of TG cells was not caused by lymphocytotoxic antibodies. The mean helper-suppressor scores for patients with PSS and DS (1.25) and those with CREST syndrome (1.36) were higher (p < 0.05) than the mean score for healthy individuals (0.80). No relationship between the immunoregulatory abnormality and the presence or titer of CICs, ANAs, hypergammaglobulinemia, or various clinical manifestations of PSS could be demonstrated in individual patients. The finding of abnormalities in T lymphocyte subpopulations and the demonstration of their altered functional expression in patients with PSS indicate that immunoregulatory mechanisms may play an important role in this connective tissue disease.