The synthesis of Hb F was studied in the BFUe-derived colonies of 20 SS patients after incubation with 35S methionine for 24 hours, 13 days after the start of the experiments. Similar analyses were made for isolated reticulocytes from 28 SS patients; these cells were incubated for 2 hours and occasionally for 24 hours. The G gamma and A gamma percentages were determined in these two Hb F preparations and in the Hb F of circulating red cells using two different HPL chromatographic procedures. The data show an increased production of Hb F in the colonies mainly of patients with low blood Hb F values. A close correlation was present between the % G gamma chain in peripheral red cells and the G gamma percentages observed for the Hb F synthesized in the BFUe-derived colonies and that in reticulocytes. However, the values for the reticulocytes were significantly higher than those for the colonies. These data indicate a considerable variability among SS patients in their ability to produce Hb F in in vitro colonies which may in part be due to differences in the numbers of BFUe types in circulation. The variation in G gamma and A gamma levels in Hb F synthesized in reticulocytes and BFUe-derived colonies could be the result of slight differences in the stability of the corresponding mRNA's.