ABSTRACTDeletion of the taurine transporter gene (taut) results in lowered levels of taurine, the most abundant amino acid in mammals. Here, we show thattaut−/−mice have lost their ability to self-heal blood-stage infections withPlasmodium chabaudimalaria. Alltaut−/−mice succumb to infections during crisis, while about 90% of the controltaut+/+mice survive. The latter retain unchanged taurine levels even at peak parasitemia. Deletion oftaut, however, results in the lowering of circulating taurine levels from 540 to 264 μmol/liter, and infections cause additional lowering to 192 μmol/liter. Peak parasitemia levels intaut−/−mice are approximately 60% higher than those intaut+/+mice, an elevation that is associated with increased systemic tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) levels, as well as with liver injuries. The latter manifest as increased systemic ammonia levels, a perturbed capacity to entrap injected particles, and increased expression of genes encoding TNF-α, IL-1β, IL-6, inducible nitric oxide synthase (iNOS), NF-κB, and vitamin D receptor (VDR). Autopsy reveals multiorgan failure as the cause of death for malaria-infectedtaut−/−mice. Our data indicate thattaut-controlled taurine homeostasis is essential for resistance toP. chabaudimalaria. Taurine deficiency due totautdeletion, however, impairs the eryptosis ofP. chabaudi-parasitized erythrocytes and expedites increases in systemic TNF-α, IL-1β, and ammonia levels, presumably contributing to multiorgan failure inP. chabaudi-infectedtaut−/−mice.