Intoxication with Ipomoea carnea has been reported in goats, sheep, and cattle in tropical regions worldwide. The disease has been characterized only in goats; therefore, the present study was conducted in sheep. Nine animals were fed feed rations that contained 3 different concentrations of Ipomoea carnea subsp. fistulosa. Individual intake varied between 10.5 and 135.2 g of fresh plant per kilogram of body weight (BW) per day. Animals first showed clinical signs between day 43 and day 63. The maximum survival time was 133 days. Sheep presented with weight loss and neurologic abnormalities. Neurologic signs were dominated by marked depression, abnormal behavior, and musculoskeletal weakness, with poorly defined motor and proprioceptive deficits. In mature animals, cytoplasmic vacuolation, consistent with accumulation of secondary lysosomes, affected neurons, astrocytes, exocrine pancreatic acinar epithelia, hepatocytes and Kupffer cells, renal tubular epithelia, thyroid follicular epithelia, cortical adrenal epithelia, endothelia and perivascular cells, and macrophages in lymph nodes and spleen. In the central nervous system, there was axonal degeneration and astrogliosis. Abortion was observed as early as day 22 of the trial. In fetal tissues and placenta of chronically poisoned ewes, cytoplasmic vacuolation was histologically detected in neurons, exocrine pancreatic acinar epithelia, hepatocytes, renal tubular epithelia, and thyroid follicular epithelia. All the sheep developed a glycoprotein storage disease, with lysosomal accumulation of N-glycosidically linked oligosaccharides, which was indistinguishable from that induced by the alkaloid swainsonine alone.