While these data point to a central role for IFN-gamma in the pathogenesis of primary HLH, a recent report by Burn et al. reveals that mice lacking expression of both perforin and IFN-gamma develop a severe HLH-like illness following LCMV infection, although the characteristics of this illness differ from those observed in animals lacking expression only of perforin. Here, IFNG is linked to hemophagocytic syndrome.