We have characterized the mononuclear cell infiltrate in the extraocular muscle of three patients with Graves' disease, using antibodies which permit staining of paraffin-embedded tissue. The majority of lymphocytes, occurring in foci or interstitially, were T cells, most of which stain for CD3 or with UCHL1. T cells few, if any, stained with SN130, directed against the CD45R determinant. This suggests that these lymphocytes comprise a recently activated population within which memory cells may reside. B cells were also found but were predominantly confined to focal aggregates, and in one patient lymphoid follicles were seen. The orbital fat and connective tissue from a further two patients contained very few infiltrating cells which were mainly UCHL1-positive. Eye muscle cells did not express Ia antigens but the interstitial cells between them were Ia-positive and the vascular endothelium in four of the five specimens also stained with Ia. These results indicate that Graves' ophthalmopathy is associated with T cell, and to a lesser extent B cell, responses against the retrobulbar tissues; the extraocular muscle interstitial cells, probably including fibroblasts, may be targets of activation resulting from this infiltration.