Evidence continues to accumulate supporting in vivo activation of T cells in scleroderma. The studies reviewed reported finding circulating cytokines in scleroderma serum or soluble T-cell membrane molecules, especially soluble interleukin-2 receptor and CD8. The antigens to which T-cell reactivity is directed, if indeed such antigens exist, remain to be identified. Specific humoral immune responses in the form of autoantibodies to nuclear-associated antigens appear to be polyclonal and antigen driven. Although autoantibodies cannot as yet be implicated in disease pathogenesis, patterns of autoantibodies are associated with, but do not reliably define, disease subsets. In patients with Raynaud's phenomenon alone, the absence of autoantibodies is predictive of not developing systemic connective tissue disease, while the presence of autoantibodies indicates an increased risk.