Sepsis and septic shock are major causes of acute renal failure (ARF). Although hemodynamic factors play a significant role in the pathogenesis of ARF during sepsis, it is now clear that nonhemodynamic factors are also extremely important. The predominant site of tissue injury in sepsis-induced ARF occurs within the proximal renal tubule. In vivo studies of the specific cellular mechanisms underlying renal injury are limited by the marked heterogeneity of the nephron. Establishing primary cultures of human proximal renal tubular epithelial cells (PTEC) provides a well-characterized in vitro model, phenotypically representative of PTEC in vivo. This in vitro system allows for investigation of the cellular mechanisms underlying proximal tubular injury during sepsis, in isolation without additional complicating cardiovascular and neuroendocrine factors.