The a andβchains of the hemoglobins A, S, Leslie and N-Baltimore have been isolated as PMB derivates by CM-cellulose and DEAE-cellulose chromatography. The relative affinities of theβA,βs,βLeslieandβN-Baltimore chains forαchains were measured through quantitation by chromatography of Che hemoglobins A and Leslie, A and S, and A and N-Baltimore that were formed when variable amounts ofαchains were added to a mixture of equal amounts of the appropriateβchains. The data indicate a greatly decreased affinity ofβLesliechains forachains; a similar preference of a chains forβAchains was observed for mixtures Involvingα,βA, andβschains, but the affinity ofβschains for a chains was higher than that ofβLesliechains. TheβN-Baltimore chains assembled with a chains at a similar rate asβAchains. The data as Interpreted Indicate that the affinity of certainβchains for a chains can be a major post-translatlonal control mechanism which regulates the level of aβchain variant in heterozygotes.