The main histopathologic features of infectious mononucleosis are described. In the lymph nodes, the principal change is the appearance of numerous large pyroninophilic cells (immunoblasts), initially expanding the paracortical zone but later extending throughout the node. Similar, large lymphoid cells appear as infiltrates in many other organs and tissues. Cells morphologically similar to Sternberg-Reed cells may be found in the lymph nodes of patients with infectious mononucleosis and other conditions apart from Hodgkin's disease. The diagnostic importance of considering not only the Sternberg-Reed cells but their milieu is stressed. A possible relationship between infectious mononucleosis and lymphoreticular malignancy is suggested by a number of observations, but a definite etiologic link is yet to be established.