Cutaneous eruptions displaying perivascular inflammatory cell infiltrates histologically may develop with the intravenous administration of cytokines. Similar findings are seen spontaneously in some patients on recovery of peripheral blood lymphocytes after profound marrow aplasia. To investigate the production of a cutaneous perivascular infiltrate further, the ability of several cytokines to induce a perivascular lymphocytic infiltrate was studied in vitro using a skin explant model. A skin biopsy specimen obtained at the time of peripheral blood lymphocyte recovery after chemotherapy-induced marrow aplasia (n = 10) was divided and incubated for 3 days with and without a series of cytokines plus various peripheral blood mononuclear cell populations. Skin incubated with interleukin 2 and granulocyte-macrophage colony-stimulating factor induced a perivascular lymphocytic infiltrate, while control samples did not. Immunophenotypic analysis revealed that the lymphocytes were predominantly CD3+/CD4+. An infiltrate was not observed when skin was incubated with cytokines alone, without the addition of simultaneously isolated peripheral lymphocytes. A perivascular pattern was not observed with the addition of interferon gamma. Only interferon gamma induced keratinocyte intercellular adhesion molecule 1 expression in experimental tissue. Certain cytokines that affect a range of cell types are capable of inducing a common cutaneous histologic pattern, the perivascular lymphocytic infiltrate.