Subacute and chronic prurigo is notoriously resistant to usual therapies. Four of five patients with a subacute or chronic form of prurigo responded well to daily intravenous injections of recombinant interferon-gamma (rIFN-gamma) (0.25-2 x 10(6) Japan Reference Unit (JRU; 1 JRU roughly corresponds to 4 NIH units) daily, for 10-14 days). In one patient examined, the dermal portion of lesional skin before the treatment contained considerable amounts of mRNA for interleukin (IL)-4, IL-5, and IL-10, indicative of infiltration of Th2 cells. Furthermore, the administration of rIFN-gamma selectively down-regulated mRNA for Th2 cytokines, IL-4 and IL-10 in peripheral blood mononuclear cells. These findings suggest that Th2 cells play a pathogenic role in these types of prurigo and that rIFN-gamma exerts its efficacy by inhibiting Th2 cells. Our pilot study suggests that the systemic administration of rIFN-gamma is a therapeutic alternative for the treatment of recalcitrant prurigo.