An open clinical trial of thymopentin was conducted on 16 children with severe atopic dermatitis. The patients were treated with injections three times a week of 50 mg thymopentin for six weeks. They were then divided randomly into two groups: group A continued thymopentin for an additional six weeks, and group B were treated with normal saline. Clinical parameters and immunological function were evaluated serially. The total severity score started to decline from baseline significantly three weeks after treatment, and continued throughout the study period in group A but began to flare up in group B two weeks after stopping thymopentin. All the eight patients in group A completed the trial but three out of eight in group B dropped out because of flaring up of skin lesion. In vitro production of interleukin-4 tended to decrease and that of interferon gamma tended to increase, but total serum IgE, in vitro IgE synthesis, and abnormally low CD8+ CD11b+ suppressor T cells remained unchanged. Histamine releasing factor (HRF), plasma histamine, and respiratory burst activities of polymorphonuclear leucocytes were appreciably decreased after thymopentin treatment. It is concluded that the clinical efficacy of short term thymopentin treatment very possibly results from the decreased production of HRF and decreased release of polymorphonuclear leucocyte derived inflammatory mediators and may have no relation with antigen-IgE immune reaction.