Red cell exchange is important in the care of acutely ill sickle-cell patients, and may be life-saving. An automated red cell exchange technique has been developed using a Baxter blood cell separator, enabling an isovolaemic exchange to be performed within 2.5 h. A total of 20 procedures have been performed in 15 patients, including one woman in the third trimester of pregnancy, with a mean decrease of 72% in the circulating sickle haemoglobin (HbS) level. This method enables almost all adult patients with sickle cell anaemia to have their HbS reduced to safe levels by only one procedure. The procedure was well tolerated by all patients, including those who were acutely ill. This technique provides an effective procedure for reducing the percentage of circulating HbS rapidly in acutely ill patients with complications of sickle cell anaemia.