A reduction of morbidity and mortality rates in homozygous sickle-cell patients was found in those with high fetal hemoglobin (HbF) levels. This factor would lead one to believe that an adequate amount of this substance would be protective to a patient with this hemoglobinopathy. This study utilizing pregnant and nongravid females, as well as males, followed for long periods of time indicates that the HbF level fluctuates with crisis. Some patients had low HbF levels with many crises and others had high amounts of HbF with no crises. However, many patients with high levels on one occasion demonstrated a decrease in HbF levels when crisis occurred. More importantly, no patient had high levels of HbF during a crisis although the amount was elevated before and after the episodes. The possible explanation and ramifications of this finding are discussed.