Lymph node sections from 12 patients with Sézary syndrome (SS) were studied histologically. The histopathologic alterations were compared with those in lymph nodes from four patients with (erythrodermatic) mycosis fungoides (MF) and two patients with a benign form of erythroderma. Most SS lymph nodes showed a rather monotonous and diffuse infiltration of cerebriform mononuclear cells (CMC), which tended to efface the normal lymph node architecture. By contrast, in lymph nodes involved by MF there was not only an increase in the number of CMC, but also a marked increase in the number of interdigitating reticulum cells that often showed a considerable degree of nuclear polymorphia. In the advanced stages of lymph node involvement by MF, blastic transformation was much more pronounced than in the SS lymph nodes. These histologic differences between MF and SS lymph nodes suggest that different pathogenetic mechanisms may be operative in the development of either of these conditions.