While MHA has been frequently reported with mechanical heart valves, hemolysis associated with native valvular heart disease is rare. A 20-year-old Amish female presented with left hip arthritis in 5/03. She had suffered rheumatic fever at age 10 manifested by Sydenham chorea, mitral regurgitation (MR) and migratory polyarthritis prompting a 5-year course of penicillin. In 5/03, she was admitted with acute arthritis of the left hip and pain in her left shoulder and hands. This picture together with a systolic murmur, pericardial friction rub and an ESR of 118 mm/h prompted a transesophageal echocardiogram (TEE) revealing a myxomatous mitral valve (MV) with severe MR and thickening of the tip of the posterior leaflet of the MV suspicious for endocarditis. Mild aortic regurgitation (AR) was also present. Blood cultures remained sterile; however, she received a course of penicillin prior to her hospital presentation. Antibiotics followed for culture-negative endocarditis. Anemia was noted with Hgb of 9.4 g/dL (12–16), HCT 27.6% (37–49), reticulocyte count 2.2%, absolute reticulocyte count 73.1 k/mcL (22–106). Serum haptoglobin was 452 mg/dL (34–234), bilirubin 0.5 mg/dL (0.2–1.2) and LDH 169 U/L (94–250). ESR was 118 mm/h (0–30). ASO was 200 IU (<200). ANA was not present. Cardiac cath demonstrating severe MR prompted a MV annuloplasty with insertion of a Duran ring in 7/03. Aortic valvular (AV) annuloplasty was also performed. No vegetations were noted. However, nodules of Arantius were prominent. In 3/04, a loud MR murmur on auscultation prompted a TEE revealing severe MR with redundant loose tissue on the atrial surface of both MV leaflets. Mild AR and moderate to severe tricuspid regurgitation were also seen. Anemia was again noted with Hgb of 10.2 g/dL. MCV was 94.2 μM3 (81–99), RDW 18.4, ESR 125 mm/h. Reticulocyte count was 9.5%. Peripheral blood smear revealed fragmented erythrocytes. Serum haptoglobin was less than 6 mg/dL, bilirubin 2.3 mg/dL, LDH 1230 U/L. Direct antiglobulin test was not reactive. PT was 14.8 sec (10.8–15.9), INR 1.2, APTT 28.6 sec (23–35), fibrinogen 611 mg/dL (174–510). D-dimer was present in concentrations greater than 0.5 mcg/mL. Vitamin B12 was 639 pg/mL (211–911). Folate was greater than 24 ng/mL (1.1–20). Homocysteine was 8.1 μM (5.0–15). Methylmalonic acid was 184 μmol/L (88–243). Serum iron was 43 mcg/dL (37–170), TIBC 334 mcg/dL (250–450) with transferrin saturation of 13%. Heinz bodies were not present. Ham’s test was without hemolysis. Lupus anticoagulant, anticardiolipin antibody, ANA, rheumatoid factor, antidouble-strand DNA, p-ANCA and c-ANCA were not present. ASO was 200 U/mL. DNA-se antibody was present at 240 (reference range less than 85). Blood cultures were sterile. On 3/18/04, she underwent AV and MV replacement with tricuspid annuloplasty. Annular dilatation was noted with diffuse inflammation suspicious for an acute rheumatic process. The Duran ring was well seated. The posterior mitral leaflet was immobilized by the diffuse inflammatory process. Histologic analysis of the valves described inflammatory changes compatible with acute rheumatic valvulitis. Following her operation, her hematologic picture became normal. On 4/26/04, Hgb was 12.1 g/dL, HCT 36.3%, bilirubin 0.8 mg/dL, LDH 265 U/L. The pattern of hemolysis appears most consistent with MHA related to acute rheumatic valvulitis with recovery following valve replacement.