Nitric oxide (NO) plays a role in many physiological and pathophysiological processes. In the kidney, NO reduces renal vascular resistance, increases glomerular filtration rate, alters renin release, and inhibits transport along the nephron. The thick ascending limb is responsible for absorbing 20-30% of the filtered load of NaCl, much of the bicarbonate that escapes the proximal nephron, and a significant fraction of the divalent cations reclaimed from the forming urine. Additionally, this nephron segment plays a role in K+ homeostasis. This article will review recent advances in our understanding of the role NO plays in regulating the transport processes of the thick ascending limb. NO has been shown to inhibit NaCl absorption primarily by reducing Na+-K+-2Cl- cotransport activity. NO also inhibits bicarbonate absorption by reducing Na+/H+ exchange activity. It has also been reported to enhance luminal K+ channel activity and thus is likely to alter K+ secretion. The source of NO may be vascular structures such as the afferent arteriole or vasa recta, or the thick ascending limb itself. NO is produced by NO synthase 3 in this segment, and several factors that regulate its activity both acutely and chronically have recently been identified. Although the effects of NO on thick ascending limb transport have received a great deal of attention recently, its effects on divalent ion absorption and many other issues remain unexplored.