Hb S polymerizes in high-density Hb SC disease erythrocytes. We hypothesized that hydroxyurea -- perhaps independent of increasing Hb F -- might reduce the density of these cells. Six Hb SC disease patients were given 1000mg of hydroxyurea daily and blood counts, cell volumes, and cell density were followed for 12 months. There was an increase in MCV and reticulocyte MCV. A fall in absolute reticulocyte counts, high-staining ('stress') reticulocytes, serum bilirubin, and an increase in the ratio of mature red cell haemoglobin to reticulocyte haemoglobin, coupled with a rise in the haematocrit inferred a decrease in haemolysis and 'stress erythropoiesis'. An improvement in cell hydration was suggested by a reduction in reticulocyte mean cell haemoglobin concentration (CHCMr), red cells and reticulocytes with CHCM > 38, and decreased dense cell counts estimated by phthalate ester and Percoll-Larex gradients. After 4-5 months treatment, Hb F rose in a few patients but the overall difference in pre- and post-treatment Hb F was not significant. A decline in cell density should diminish the polymerization tendency of Hb S in Hb SC disease.