Most of the earlier clinicopathologic studies of orbital and conjunctival lymphoid infiltrates were done before the development of immunohistologic methods. In this study, we have examined 99 lymphoid infiltrates of the orbit and conjunctiva immunohistologically and correlated clinical and histologic features with immunophenotype. Sixty-six infiltrates expressed monotypic immunoglobulin; one case was immunoglobulin-negative, B-lineage; and 32 infiltrates expressed polytypic immunoglobulin. Using histologic criteria, 36 cases were malignant (35 monotypic; one immunoglobulin-negative, B-lineage), 44 were indeterminate (31 monotypic, 13 polytypic), and 19 were benign (all polytypic). Combining histologic and immunophenotypic criteria, 67 cases were diagnosed as malignant lymphoma. Seventy-six percent of the lymphomas were classified as low-grade according to the Working Formulation; small lymphocytic lymphoma (45%) was the most common histologic subtype. Cytologic atypia (p less than .0001) and Dutcher bodies (p less than .05) were found only in lymphomas. Similarly, bilateral involvement (p less than .05) and dissemination at time of presentation (p less than .001) occurred only in lymphomas. No other histologic or clinical features reliably distinguished lymphomas from benign orbital and conjunctival lymphoid infiltrates. Nineteen patients had a prior history of extraorbital malignant lymphoma, and eight patients had a history of pseudolymphoma. Patients with a history of malignant lymphoma more often presented with dissemination (p less than .001) and less often had the small lymphocytic subtype (p = .07) than patients without a history of lymphoma. However, not all patients with a history of extraorbital lymphoma had monotypic orbital and conjunctival infiltrates, and the incidence of monotypic orbital and conjunctival lesions in these patients was similar to that of the patients without a history of lymphoma. Patients with a history of pseudolymphoma always presented with localized disease (p less than .01) and more often had benign lesions (p = .08) as compared with patients without a history of pseudolymphoma. We conclude that the presence of either cytologic atypia or Dutcher bodies is a reliable criterion of malignant lymphoma in the orbit and conjunctiva. However, for one-third of the cases in this study, immunohistologic studies were the only means of distinguishing malignant from benign lymphoid infiltrates.