Whether Graves' ophthalmopathy is the results of a cell-mediated or humoral autoimmune response is controversial. T-Lymphocytes that regulate these two mechanisms, Th1 and Th2, respectively, are characterized by the profile of cytokines that they secrete. We, therefore, investigated the spectrum of T-lymphocyte cytokines expressed in Graves' orbital tissue by means of the polymerase chain reaction using reverse transcribed mRNA as template. From three Graves' thyroid tissues (positive controls), we obtained DNA products of the predicted size for the Th1 cytokines interferon-gamma (IFN gamma) and interleukin-2 (IL-2) as well as for Th2 cytokines IL-4 and IL-5. A signal for IL-10 (Th1 and Th2) was also detected. No cytokine signals were observed in peripheral blood (negative control). Despite the presence of T-cells (CD3 delta marker) in the orbital connective tissue/fat of all five patients studied as well as in orbital muscle from one of these patients, IFN gamma reverse transcribed mRNA was notably absent from these tissues. In contrast, IL-2, IL-5, and IL-10 cDNA was present in orbital tissues from one or more patients. Of particular importance, an IL-4 signal was detected in orbital connective tissue/fat of patients 6 and 7 as well as in muscle of patient 7. The balance between IL-4 and IFN gamma determines whether an immune response is predominantly humoral or cell mediated. Our finding of IL-4, but not IFN gamma, mRNA expression in orbital tissue supports a role, at least in some patients, for humoral autoimmunity in Graves' ophthalmopathy.