A method is described for the separation of blood and bone marrow leukocytes on the basis of buoyant density, using a discontinuous Ficoll-Hypaque density gradient. The median cell densities of monocytes and lymphocytes were found to be 1.067–1.077 and 1.073-1.077 g/ml, respectively. The cells of the myeloid series were shown to increase in density with maturation; the myeloblasts had the lowest density (1.064- 1.065 g/ml) and the neutrophils the highest (greater than 1.080 g/ml). Cell volumes have been determined on isolated cell populations. The findings were: monocytes, 534 +/- 47 cu mu; lymphocytes, 247 +/- 18 cu mu; and neutrophils, 468 +/- 24 cu mu. Fourteen patients with acute lymphoblastic leukemia were studied. In four patients, the lymphoblasts were of low density (less than 1.068 g/ml), whereas the remaining patients had high density (greater than 1.068 g/ml) lymphoblasts. These four patients had large numbers of lymphoblasts in the peripheral blood and a poor prognosis. Lymphoblast volumes were not different in these two groups and were unrelated to prognosis.