Twenty-nine patients with systemic scleroderma (SSD), whose lymphocytes significantly responded to a scleroderma-inducing glycosaminoglycan-associated antigen (stimulation index greater than or equal to 1.7), were separated into the two groups of marked and moderate responses, according to the mitogenic response of their peripheral lymphocytes. A marked response, with a [3H]-thymidine uptake of +3 SD over the mean of unstimulated SSD lymphocytes, was seen in severely affected patients with a high OKT4/OKT8 ratio. In contrast, the lymphocytes of patients with benign disease responded moderately to the antigen, showing lower thymidine uptake by both unstimulated and stimulated lymphocytes. This latter group had a high frequency of elevated anti-nRNP antibody.