A second instance of the unstable mutant Hb Nottingham (α;2β;2(FG5) 98 Val→Gly) is reported in a 7-year-old boy. Because of splenomegaly, cholelithiasis, and frequent episodes of abdominal pain, he underwent a splenectomy and cholecystectomy at age 6. The surgery resulted in both an amelioration of his RBC destruction and an acceleration of his rate of growth.Biosynthetic studies were carried out using reticulocytes obtained from his peripheral blood. These analyses disclosed an exceedingly high specific activity ratio for Hb N/Hb A. In addition as the incubation proceeded, more radioactivity accumulated in theα; chain fraction than in theβ; chains (β;A+β;N). This observation is presumed secondary to degradation of the unstableβ;Nchains.