The renal medulla contains more mRNA of the inducible isoform of nitric oxide synthase (iNOS) than the cortex, which may be important in preventing ischaemic injury, since blood flow and tissue oxygen tension are normally low in this region. We examined the effects of the bacterial endotoxin E. coli lipopolysaccharide (LPS) on renal function and regional expression of iNOS in male Sprague-Dawley rats. In six rats, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were 0.95 ± 0.09 ml min-1 g-1 and 3.36 ± 0.20 ml min-1 g-1, respectively, and decreased significantly to 0.35 ± 0.09 and 1.74 ± 0.54 ml min-1 g-1, respectively, 1 h after administration of LPS. In an additional seven rats, GFR and ERPF were 0.91 ± 0.07 and 2.97 ± 0.30 ml min-1 g-1, respectively, 18 h after LPS administration; these values were similar to those in control rats. In all rats, arterial pressure was stable throughout all study periods. In control rats, immunoblot analysis revealed expression of the iNOS protein in the cortex and more pronounced expression in the medulla. In rats studied 18 h after LPS treatment, there was a striking increase in the iNOS expression in the outer medulla. Immunohistochemical examination in the LPS-treated rats showed limited iNOS immunostaining in the cortex, localised to the vascular endothelium and macula densa; however, intense and widespread staining was noted in the tubular and vascular structures of the outer medulla. These findings demonstrated a differential constitutive expression of iNOS protein in different regions of the rat kidney, and marked augmentation of iNOS expression in the outer medulla by LPS. Experimental Physiology (2002) 87.2, 153-162.