T-cells are involved in the pathogenesis of cutaneous drug reactions. T-cell phenotype and cytokine release pattern in rivo and in vitro might correlate with the type of immune response involved in cutaneous drug reactions. In vitro release of interferon-gamma and macrophage migration inhibition factor (MIF) from peripheral blood lymphocytes, following in vitro challenge with the suspected unmodified drugs, was studied in 12 patients with drug-induced urticaria and/or angioedema and in two group-matched controls. The occurrence of positive interferon-gamma and MIF responses was significantly higher in patients with drug-induced urticaria and/or angioedema than in controls. The sensitivity and specificity of the interferon-gamma test (50% and 92%, respectively) were similar to that of the MIF test (58% and 96%, respectively). Percentage agreement between both tests was 80.9 (kappa = 0.76). In vitro release of interferon-gamma and MIF in drug-induced urticaria and/or angioedema suggests a drug-specific immune response, and may implicate the drug as a possible inducer of the reaction.