We have previously demonstrated that peripheral blood mononuclear cells from patients with Sézary syndrome, the leukemic form of cutaneous T-cell lymphoma which is accompanied by erythroderma and lymphadenopathy, have a Th2 cell cytokine [interleukin 4 (IL-4) and interleukin 5] production pattern. In this study, we extend these observations to demonstrate a correlation of the presence of a Th2 cytokine pattern with a malignant T-cell clone in different stages of cutaneous involvement among patients with cutaneous T-cell lymphoma (CTCL). Skin biopsies were obtained from 12 CTCL patients with various disease stages (three patch, three plaque, six tumor), three patients with parapsoriasis, four patients with inflammatory dermatoses, including two psoriasis and two lichen planus, and 12 normal controls. Total RNA was extracted, reverse transcribed, and PCR amplified with IL-2, IL-4, IL-5. interferon gamma (IFN-γ, and β-actin oligonucleotide primers. Although all skin specimens tested had detectable IL-2 and IFN-γ mRNA, only specimens from patients with CTCL or parapsoriasis had demonstrable IL-4 and/or IL-5 mRNA. Specifically, IL-5 mRNA was detected in skin biopsies from five of six tumor-stage CTCL, two of three plaque-stage CTCL, one of three patch-stage CTCL, and 1 of 3 parapsoriasis patients, whereas IL-4 mRNA was demonstrated to be present in five of six tumor-stage, one of three plaque stage, none of three patch-stage CTCL, and none of three parapsoriasis patients. These results indicate that in all stages of cutaneous involvement of CTCL, encompassing patch stage through tumor stage, IL-4 and IL-5 mRNA is variably detectable. In tumor-stage skin lesions, typically characterized by a dense dermal infiltrate of malignant T cells, Th2 cytokine mRNA is virtually always detectable. The ability to detect Th2 cytokine mRNA in the skin of patients with CTCL supports our previous findings that the malignant T cells in CTCL posses a Th2-helper cell phenotype.