Twenty-three patients with angiocentric immunoproliferative lesions (AILs) including angiocentric lymphoma were evaluated clinically and pathologically. Pathologic subclassification performed without knowledge of the clinical outcome divided the cases into three histologic grades on the basis of cellular atypia and degree of inflammatory background. Immunophenotypic studies of lesions from six patients demonstrated a mature T-cell phenotype with a predominance of CD4-positive cells. Abnormalities of antigenic phenotype were demonstrated in only one case, classified as grade III. That tumor also demonstrated a clonal rearrangement of the T beta gene. Progression to malignant lymphoma following initial immunosuppressive therapy with cyclophosphamide and prednisone occurred in three of nine patients with grade I lesions and four of six patients with grade II lesions. The supervening lymphomas were usually refractory to subsequent aggressive chemotherapy, with only one patient achieving a complete remission. In contrast, seven of eight patients with grade III lesions achieved a complete remission with aggressive combination chemotherapy, two of whom also received supplemental radiation therapy. These studies support the concept that the AILs represent a spectrum of post-thymic T-cell proliferations. The single most important prognostic indicator for ultimate survival is achievement of an initial complete remission. Patients treated initially with conservative chemotherapy may be compromised in their ability to achieve a complete remission if they progress to a higher grade lesion.