Globin synthesis studies are useful in the analysis of thalassemia syndromes. We have applied globin synthesis and free alpha-chain pool studies of peripheral blood to characterize hematologic disorders where alpha- or beta-thalassemia was present in combination with HbS or HbC. In 60 non-thalassemic controls, the beta/alpha specific activity ratio was 1.01 +/- 0.06 (SD). In three patients with HbS-beta0-thalassemia, the (betas + gamma)/alpha ratios were 0.48-.067. In four patients with HbSS-alpha-thalassemia, the (BETAS/ALPHA RATIO was 1.26 +/- 0.18 (1.13- 1.53). The radioactive free alpha-chain pool in three patients with HbS- beta0-thalassemia was elevated (35.1%-53.0%), while three patients with HbSS-alpha-thalassemia had decreased free radioactive alpha-chain pools (3.2%-6.4%); both were significantly different from the mean (15.1% +/- 2.6%) of the 17 iron-sufficient controls. Simultaneous studies of the fraction of newly synthesized alpha chain contained in the free alpha- chain pool in peripheral blood and bone marrow demonstrated that this fraction was larger in peripheral blood than in marrow, and that the differences between thalassemia patients and controls previously found in bone marrow using these methods were also present in peripheral blood. The results indicate that even when family studies are not possible, patients with HbS in combination with alpha- or beta0- thalassemia can be differentiated from those with homozygous sickle cell disease by globin synthesis and free alpha-chain pool studies using peripheral blood.