The authors studied the occurrence of peanut aalutinin (PNAkbinding cells in paraffin-embedded specimens of 145 patients with Hodgkin's disease (HD). The staining reaction of lymphocytes was consistently negative. A positive staining reaction was observed in two types of cells: macrophagehistiocytes (M-H), and Reed-Sternberg (R-S) cells and their variants. Diffuse or globular cytoplasmic staining was found in M-H, which was easily distinguished from a unique "cell surface and cytoplasmic,' staining pattern of R-S and related cells. Thus defined, M-H were numerous in lymphocyte depletion and mixed cellularity, less common in lymphocyte predominance, and least frequent in the nodular sclerosis type. Numerous M-H correlated with B-symptoms and a poor response to therapy. Among the asymptomatic patients with localized disease at presentation, the presence of large numbers of M-H was associated with a high incidence of relapse within 2 years of therapy. These findings suggest that the number of non-neoplastic M-H in H D may be an important determinant in the clinical presentation and course of disease. Peanut agglutinin staining may be useful for the detection of M-H in routine diagnosis and classification of HD, which has not been feasible by conventional methods.