Paraffin-embedded lung wedge biopsy specimens from 14 patients with pulmonary lymphomatoid granulomatosis (LYG) were analyzed using immunoperoxidase stains specific for T cell- and natural killer cell-associated antigens. Nine cases had a minor population of CD20+ large B-cells (B-cell LYG) amidst a background of CD3- and betaF1-immunoreactive T cells. In 8 of the 9 B-cell LYG cases, the majority of the background T lymphocytes had a cytotoxic phenotype as defined by the expression of CD8 and the cytotoxic granule proteins TIA-1 (granule membrane protein 17) and granzyme B. Five cases lacked CD20+ large cells and, instead, showed predominantly CD3+ and betaF1 + T cells (T-cell LYG). Whereas the small, medium, and large atypical lymphocytes were all positive for CD3 and betaF1 in the T-cell LYG cases, immunoreactivity for CD8, TIA-1, and granzyme B was limited to the small lymphocytes, with a distribution indistinguishable from that seen in B-cell LYG. These findings indicate that LYG is composed of a heterogeneous group of lymphoproliferative disorders that share, as unifying features, a relative paucity of neoplastic cells and a prominent reactive infiltrate rich in cytolytic lymphocytes.