Sickle cell disease (SCD) is one of the commonest inherited diseases, affecting millions of people, particularly in Western Africa but also in the Caribbean, USA and Northern Europe. A simple mutation in the β haemoglobin gene produces HbS, rather than the normal HbA. Most patients are the homozygous HbSS-type, but heterozygotes also display symptoms eg HbSC and HbS-thalassaemia. Deoxy-HbS is less souble and able to form rigid polymers which distort the red cell into bizarre shapes, also producing other sequelae which include increased membrane permeability. The resulting pathology is complex and extensive, involving anaemia and vaso-occlusive episodes, hence pain and organ damage. Early diagnosis is critical to manage and ameliorate the common manifestations of SCD (Steinberg, 2001). The increased membrane permeability of sickle cells involves several pathways (Lew & Bookchin, 2005): KCl cotransport, a deoxygenation-induced non-selective cation pathway(P_sickle) and the Gardos or Ca²⁺-activated K⁺ channel. K⁺ loss via these pathways induces cells to shrink. The rise in [HbS] makes sickling more likely, with other changes including phospholipid scrambling. P_sickle plays a central role by allowing Ca²⁺ entry, activating the Gardos channel. Although the principle defect is mainly increased cation permeability, sickle cells lyse in isosmotic non-electrolyte solutions when deoxygenated in N₂ (Browning et al 2007). Lysis is accompanied by entry of non-electrolye into the cells. Here we have developed a simple haemolytic test for diagnosing SCD, which utilises this phenomenon. Sickle red cells were washed in MOPS-buffered saline (145mM NaCl, 5mM glucose, 10mM MOPS, pH 7.4) and re-suspended in isosmotic sucrose solution (replacing NaCl with sucrose). They were deoxygenated with sodium metabisulphite (4%) rather than by reduction in O₂ tension. After 30 min incubation, unlysed red cells were removed by centrifugation. Haemolysis was determined using Hb measurement as optical density at 540nm or by eye. Under these conditions, in samples from 33 SCD patients (both HbSS and HbSC), haemolysis was present in 29 (88%), compared with 1 in 13 (8%) for normal red cells. The ability to deoxygenate chemically, using haemolysis as a simple measure of increased permeability of sickle cells represents an important step towards developing a novel and practical diagnostic test for SCD, amenable for use in less developed areas of the world. In addition, it also appears that metabisulphite which oxidises the bulk of the haemoglobin to methaemoglobin with its oxy-configuration also supports a permeability change hitherto observed under conditions of low O₂ tension when Hb will be in the deoxy-form.