Lymphomatoid papulosis (LyP) is a papulonodular skin eruption characterized by spontaneous regression. In order to evaluate the role of host immune reactions in the phenomenon of regression, we analyzed skin biopsies from various stages of evolution in 16 patients with LyP using morphologic and immunoperoxidase techniques. Both rapidly regressing type A and more chronic type B lesions of LyP had modest perivascular and lesional infiltrates of small helper and suppressor T lymphocytes as well as histiocytes. Type A lesions in addition to numerous neutrophils and eosinophils had a more extensive lymphocytic infiltrate than type B lesions. Natural killer cells were not prominent in the skin lesions, although several patients had increased numbers of circulating natural killer cells. Our results demonstrate a correlation between the inflammatory components found in skin biopsies from patients with LyP and clinical behavior and suggest that cell-mediated immune reactions may play a role in the spontaneous regression of LyP.