Tissue sections from involved and uninvolved skin of nine patients with atopic dermatitis (AD) were investigated by light microscopy, electron microscopy, and an immunoperoxidase method using monoclonal antibodies to cell-surface antigens. Acute lesions were characterized by spongiotic epidermis, with increased numbers of infiltrating mononuclear cells consisting predominantly of lymphocytes. Perivascular dermal infiltrates consisted of lymphocytes and a few monocytes-macrophages. Capillary endothelial cells were not enlarged. In chronic lesions the epidermis was hyperplastic, with virtually no cellular infiltrate. The perivascular dermal infiltrates consisted primarily of monocytes-macrophages intermixed with lymphocytes. Capillary lumens were narrowed by enlarged endothelial cells. The majority of the infiltrating lymphocytes in all skin biopsy specimens from AD patients were stained with anti-T3, anti-Leu-1, anti-T4, and anti-Leu-3 antibodies, suggesting that most of the infiltrating lymphocytes were T cells possessing the helper/inducer phenotype. In contrast, a smaller number of infiltrating cells reacted with anti-T8 or anti-Leu-2 antibodies, which define the suppressor/cytotoxic T cell population. Langerhans cells, as defined by reactivity with anti-T6 monoclonal antibody, were increased in the diseased skin of AD patients. The presence of increased numbers of Langerhans cells and T cells of the helper/inducer phenotype may reflect increased antigen processing in the diseased skin of patients. In addition, the smaller number of T8+ cells infiltrating into the skin suggests that the depression of circulating T8+ cells observed in the majority of patients with AD is not due to the selective migration of these T8+ cells into the skin.