BACKGROUND Little is known about hereditary spherocytosis (HS) and hereditary elliptocytosis (HE) in the native population of Saudi Arabia, even though these conditions are seemingly common. The purpose of this study was to ascertain the protein make-up of the red cell membrane in healthy Saudis and in patients with HS and HE. METHODS Eighteen healthy Saudi subjects (13 males and 5 females), 11 patients with HS (6 males and 5 females) and 11 patients with HE (7 males and 4 females) were studied. All normal controls and patients underwent SDS-PAGE red cell membrane protein analysis in duplicate and the stained protein bands were identified and quantitated by densitometry. RESULTS In normal, healthy Saudis, the mean values for seven membrane proteins ( I+/- spectrin, I(2) spectrin, ankyrin, band 3, protein 4.1, protein 4.2, and actin) were similar to those published for normal, healthy Americans. Of the eleven cases with HS, 7 (64%) demonstrated detectable protein abnormalities while 4 (36%) were apparently normal. The electrophoretic patterns of membrane proteins in Saudis with HS differed from those of patients with HS in other parts of the world. Of the 11 cases of HE, 7 (64%) displayed abnormalities while 4 (36%) were normal. CONCLUSIONS The electrophoretic pattern of the main proteins in the membranes of red blood cells in healthy Saudis is similar to that reported from the USA. However, significant differences exist in the electrophoretic patterns between Saudi patients with HS and patients from other parts of the world.