Mild anemia can occasionally be observed during viral hepatitis, but severe hemolysis has previously only been reported in a few patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We report a case of massive acute hemolysis associated with an acute hepatitis A in a 39-year-old woman in the absence of G6PD-deficiency. The patient was also suffering from mild rheumatoid arthritis. All known factors responsible for hemolysis were ruled out. Although tests for autoimmune hemolytic anemia were negative the patient made a dramatic recovery after treatment with corticosteroids, suggesting an immune mediated mechanism nonetheless.