Clinicopathologic analysis of 400 ocular adnexal lymphoid neoplasms has demonstrated that the orbital lymphoid neoplasms occur primarily in the sixth and seventh decades of life; that their benignancy or malignancy is generally indistinguishable clinically; that the orbital malignant lymphomas are most commonly small cell lymphomas; that the orbital "histiocytic" lymphomas almost always represent an anomalous deposit of disseminated lymphoma; and that the percentage of patients with orbital lymphoma who develop systemic disease varies with the histopathology: two thirds of cases of poorly differentiated lymphocytic lymphomas, as defined cytomorphologically, have associated systemic disease. Prospective correlative clinicopathologic and immunologic analysis of 25 cases has shown that cell marker analysis divides the ocular adnexal lymphoid infiltrates into immunologically polyclonal proliferations, which show diverse but benign histopathologic features, and immunologically monoclonal B cell proliferations, which have the histologic features of malignant lymphomas. The benign, polyclonal ocular pseudolymphomas recapitulate the cell marker profile of a benign reactive lymph node with similar variations in the T cell:B cell ratio. The ocular adnexal and nodal B cell lymphomas are analogous in that they most commonly express surface IgM heavy chains and kappa light chains, express Ia antigens in parallel with SIg, and occasionally contain neoplastic B cells at various developmental stages--i.e., Ia+SIg+ and Ia+SIg-. Correlative immunologic and ultrastructural studies have demonstrated that electron microscopy is a reliable and reproducible technique for indirectly assessing the mono- or polyclonality of an ocular adnexal lymphoid neoplasm. This study is focused on the use of hybridoma-derived monoclonal antibodies, which are capable of detecting maturational stages of B and T cell differentiation and functionally distinct T cell subsets, in order to investigate the interactional and immunoregulatory defects that participate in the generation of the ocular adnexal lymphoid proliferations.