Activated cell-mediated immunity is accompanied by elevated concentrations of interferon-gamma leading to the secretion of neopterin-derivatives which are known as sensitive immune activation markers in clinical laboratory diagnosis. Recent data imply a potential role of neopterin-derivatives in oxygen-free radical-mediated processes and a direct impact of 7,8-dihydroneopterin on tumor necrosis factor alpha-mediated programmed cell death. We report here that 7,8-dihydroneopterin and hydrogen peroxide upregulate the production of interferon-gamma, thereby establishing an autocrine feed-back loop. Data put emphasis on the role of neopterin-derivates within the cytokine network.