We studied the effects of Narthecium ossifragum on goat kidneys. Twenty-five Norwegian dairy goats, 5 weeks to 4 months of age, were orally dosed with an aqueous extract from N. ossifragum. In experiment 1, we studied microscopic and functional changes in 12 animals that were euthanatized 2, 3, 4, 5, and 6 days after treatment. In experiment 2, we included ultrastructural studies on serial renal biopsies and urine analysis from five extract-treated animals and two controls. In addition, urine samples were collected from four dosed and two control goats. Ultrasonography revealed perirenal and retroperitoneal fluids. Microscopic changes were observed after 6 hours. The findings, most obvious in the inner cortex and the outer medulla, consisted of cytoplasmic vacuolization, interstitial edema, and focal necrosis of tubular epithelial cells. Ultrastructurally, the tubules had loss of microvilli, irregular cytoplasmic vacuolization, mitochondrial swelling with loss of cristae, and irregular but continuous basement membranes even with necrosis. In the glomeruli, there were occasional endothelial damage and shortening and swelling of the foot processes. Peritubular capillaries had breaks in the vessel walls and irregular endothelial cell edema, and the interstitium had marked edema. The functional lesions included elevated serum urea, creatinine, and magnesium concentrations, a slight decrease in serum calcium concentration, elevated urine protein and urine protein-creatinine ratio, and increased activities of urine alkaline phosphatase and gamma glutamyl transferase. Our findings indicate a fast-acting toxic principle inducing damage by both direct toxic and secondary ischemic effects.