ABSTRACT A 27-year-old female with sickle cell disease (HbSS) was admitted presenting with severe bone pain and fever. She refused blood transfusions throughout her hospital stay for religious reasons. During the first 9 days of admission, the patient's clinical presentation became worse despite antibiotic coverage. The patient exhibited pulmonary infiltrates and mild hypertension, increased pain, fever, tachycardia, and decreased hematocrit. After day 8 of admission, her laboratory findings and clinical presentation indicated that her disease was markedly worse. With the patient's consent, inhaled nitric oxide therapy (iNO = 40 ppm) was initiated and continued for 3.2 days. After a full day of iNO therapy, the clinical improvement was limited to temperature normalization and stabilization of her hemoglobin levels. After 2 more days of iNO therapy, her multiple clinical complications of sickle cell disease improved markedly and she was discharged 3 days after completion of the iNO treatment. The complications of NO therapy, such as methemoglobulinemia or decreased blood pressure, were not detected during the iNO therapy. Although limited to a single individual, we propose that our anecdotal experience suggests that iNO therapy may (i) need to be continuous for several days to provide improved benefits, (ii) treat several of sickle cell complications besides pain, and (iii) exhibit few complications. These proposals need to be confirmed in clinical trials.