A 20-year-old man has been under observation for 18 years because of unstable hemoglobinemia, Hb Buenos Aires, Bryn Mawr (beta-globin, Phe85Ser). At the age of 19 years, he was hospitalized because of fever and hemolytic crisis, and the symptoms resolved after infusion of antibiotics. Nucleotide sequencing of the beta-globin gene confirmed that the patient was heterozygous for the mutation. The patient's erythrocytes showed an increased affinity for oxygen and a prolonged glycerol lysis time. We review a previously reported single family and 5 other cases, and discuss the clinical significance of splenectomy and plasma-derived haptoglobin.