Three patients with ankylosing spondylitis developed renal papillary necrosis. All had received prostaglandin synthetase inhibitors including phenylbutazone, indomethacin, or ibuprofen. One patient had sickle trait. These drugs are not commonly associated with papillary necrosis in man, but may adversely effect renal medullary blood flow. An underlying renal vascular abnormality related to ankylosing spondylitis is also considered. Patients with ankylosing spondylitis who are taking prostaglandin synthetase inhibitors should be routinely screened for hematuria.