Salmonella enterica serovar Typhimurium (S. Typhimurium) induces a unique form of cell death called pyroptosis in host macrophages, which is characterized by caspase-1-dependent pore formation and osmotic lysis. DNA fragmentation during pyroptosis results from caspase-1-stimulated nuclease activity, but is not mediated by poly(ADP-ribose) polymerase (PARP) activation or DNA fragmentation. Membrane pores with diameters between 1.1 and 2.4 nm form during pyroptosis and cause cell swelling and lysis. These pores require host cell actin cytoskeleton rearrangements, caspase-1 activity, and the bacterial type III secretion system (TTSS). However, insertion of functional TTSS translocins into the host membrane is insufficient to directly evoke pore formation. Inflammatory cytokines, such as IL-1β and IL-18, are released from infected macrophages during pyroptosis, but this release does not require cell lysis. The findings provide additional evidence supporting pyroptosis as a novel pathway of inflammatory programmed cell death.Salmonella enterica serovar Typhimurium (S. Typhimurium) induces a unique form of cell death called pyroptosis in host macrophages, which is characterized by caspase-1-dependent pore formation and osmotic lysis. DNA fragmentation during pyroptosis results from caspase-1-stimulated nuclease activity, but is not mediated by poly(ADP-ribose) polymerase (PARP) activation or DNA fragmentation. Membrane pores with diameters between 1.1 and 2.4 nm form during pyroptosis and cause cell swelling and lysis. These pores require host cell actin cytoskeleton rearrangements, caspase-1 activity, and the bacterial type III secretion system (TTSS). However, insertion of functional TTSS translocins into the host membrane is insufficient to directly evoke pore formation. Inflammatory cytokines, such as IL-1β and IL-18, are released from infected macrophages during pyroptosis, but this release does not require cell lysis. The findings provide additional evidence supporting pyroptosis as a novel pathway of inflammatory programmed cell death.