This report describes T cell lines derived from a patient with subacute cutaneous lupus after treatment with intravenous pulse cyclophosphamide. We selected for mitotically active, hypoxanthine-guanine phosphoribosyltransferase-deficient (HPRT-) T cells, by culture in a selective medium containing 6-thioguanine. When HPRT- cell lines were derived 6 days after pulse cyclophosphamide (CYC) treatment, they were predominantly CD8+ and T cell receptor (TCR) gamma/delta+, producing interferon-gamma (IFN gamma). Cell lines derived 21 days after CYC treatment were CD4+, TCR alpha/beta+ and produced both IFN gamma and interleukin-4. These results support a possible role for gamma/delta+ T cells in subacute cutaneous lupus and suggest a mechanism for the therapeutic effect of CYC.