Globin chain synthesis analysis was introduced in the study of thalassaemia syndromes more than 30 years ago (1). It has greatly contributed to the understanding of the pathophysiological mechanisms of the different thalassaemia syndromes. Moreover, even in the DNA era it still remains a very sensitive diagnostic tool, very useful to define some complex or atypical forms of thalassaemia.

There are two established methods for globin chain synthesis analysis described in this chapter: one is the first classical method of Weatherall and Clegg, based on carboxymethyl cellulose chromatography for globin chain separation, the other is based on reversed phase high performance liquid chromatography (HPLC) (2). Finally a rapid method using vertical isoelectric focussing is described. The three methods described below use some common methodologies including white cell removal, reticulocyte enrichment, incubation with amino acids and radioactive tritiated leucine. However the main difference in the three methods is the methodology of separating the globin chains. The protocols are described in full for each method despite the overlap.