Several lines of evidence indicate that Hb M Saskatoon (β63 His→Tyr) may be slightly unstable.In vivostudies have shown that heterozygotes for this variant have a slight b u t constant hemolysis (1-3), and, in one case, the hemolysis was markedly accelerated by the administration of a sulfonamide drug (3). In addition, Hayashi et al. have demonstratedin vitrothat Hb M Saskatoon is less stable than Hb A on exposure t o heat or to sodium benzoate (4). We have examined the biosynthesis of this variant to determine the degree of instability of the abnormalβchain. Unstableβchain variants are usually synthesized a t a normal rate. However, because they are more likely to be degraded than normalβchains, they constitute less than 50% of the totalβchain in peripheral blood and have higher specific radioactivities thanβA, as recently reviewed. (5)