We report 11 consecutive cases of erythroderma, a high percentage of which were associated with the growth of Staphylococcus aureus in cultures from blood, joint fluid or skin. In biopsies from all the patients we found close morphological associations between lymphocytes and endothelial cells, with some of the lymphocytes showing features of blastoid transformation to T helper lymphocytes. In extreme cases, sheets of T cells, including T helper lymphocytes, formed a syncytium with endothelial cells in the dermis. Marked capillary proliferation was noted both on light and electron microscopy. We suggest that erythroderma is precipitated by antigens such as protein A, a potent T cell mitogen present on the cell surface of Staphylococcus aureus, or by drugs, such as phenytoin. These antigens induce antigen presentation by individual endothelial cells, leading to T helper transformation and lymphocyte proliferation. Endothelial proliferation resulting from lymphocyte-endothelial interaction results in the vascular proliferation associated with this syndrome.