Apoptosis has been implicated as an important mediator of immunosuppression associated with a depleted nutritional state. Since a number of cytokines are likely to influence the rate of apoptosis, we determined the effect of interferon-gamma (IFN-${gamma}$) on apoptosis of macrophages in serum/amino acid deprived cell culture conditions. IFN-${gamma}$ further increased the rate of apoptosis compared to trophically stressed macrophages. In addition, we showed that enhancement of apoptosis by IFN-${gamma}$ is caused by a decrease in mitochondrial membrane potential due to upregulation of p53 and Bax and down-regulation of Bcl-xL. Moreover, we found that IFN-${gamma}$ increases caspase-3 activity that had been induced by serum/amino acid depletion, and that JAK1 signaling is involved in capase-3 activation and in the enhancement of apoptosis by IFN-${gamma}$.