OBJECTIVES--To examine the expression of the natural killer (NK) antigen CD56, and T cell receptor delta chain antigen (TCR delta), expressed on the gamma delta T cell subset, in patients with scleroderma, and to correlate levels of expression with clinical characteristics. METHODS--Peripheral blood mononuclear cells (PBMCs) from 15 patients with scleroderma and 11 controls were obtained from heparinised blood on a ficoll/hypaque gradient, stained with monoclonal antibodies, and examined by flow cytometry for expression of CD56 and TCR delta. RESULTS--Overall, the proportion of PBMCs expressing CD56 in the patient group (14.4 (SEM 2.6)%) was not significantly different from controls (8.75 (2.6)%). The greatest levels of expression were found in patients late (more than three years) in their disease course (18.1 (3.3)%) and in patients who did not express anti-Scl-70 antibodies (17.1 (3.5)%). The proportion of gamma delta T cells was significantly lower in the patient group (1.61 (0.52)% v control 2.61 (0.46)%) (p < 0.05). Patients early in their disease or with anti-Scl-70 antibodies accounted for the reduction in gamma delta T cells (0.71 (0.29)% and 0.96 (0.41)% (p < 0.01 and p < 0.05, respectively). CONCLUSIONS--This study emphasis that NK and gamma delta T cell numbers vary depending upon patient characteristics and may help explain prior contradictory reports. Decreased numbers of gamma delta T cells were seen in scleroderma patients, especially those with anti-Scl-70 antibodies and a disease duration of less than three years.