Fetal hemoglobin (HbF) in adult life is usually restricted to a few erythrocytes called F-cells. Their presence can be detected and the quantity of HbF per F-cell estimated by pericellular immunodiffusion reactions with anti-HbF. In normal adults F-cell frequency (range: 1 F-cell per 25 erythrocytes to 1 per 6800) and the mean amount of HbF per F-cell (range: approximately 14 to 28% of mean cell hemoglobin), although they are variables, remain constant over many months. Frequencies are similar in men and women. For a given individual, F-cell lifetimes are probably similar to those of other erythrocytes. F-cell production is not appreciably influenced by short term exposure to high altitude (approximately 4300 m) hypoxia. F-cell frequencies are briefly but substantially increased in many women during midpregnancy. In some women, presumptive 5- to 15-fold increases in F-cell production result in observed 3- to 7-fold increases in F-cell frequency during the 23rd to 31st weeks of gestation. These increases in F-cell frequency arise from selective alterations in maternal erythropoiesis and not from transplacental bleeding from the fetus. Substantial increases in F-cell frequency also occur in most adults with acute leukemia. In both pregnancy and leukemia, F-cell contributions of HbF are sufficient to account for modest elevations found in hemolysate HbF levels.