There is evidence from both in vivo and in vitro studies that the synthesis of hemoglobin can be modified by posttranslational alterations in the assembly of the tetrameric molecule. Globin biosynthesis in reticulocytes of patients with sickle cell disease was studied to ascertain the effects of lead and ethanol on gamma-globin chain synthesis and hemoglobin assembly. In incubations containing lead (400 micrograms/dl) or ethanol (1.0 M) there were 86.7 +/- 139.7% and 542.7 +/- 397.0% increases in the relative synthesis of the gamma-globin chain. This was associated with a relative reduction in alpha-chain synthesis, as estimated by changes in the alpha/gamma + beta S synthesis ratio, as well as a marked reduction in total globin synthesis.