The influence of haemoglobin genotype on the response to iron supplementation was studied in a randomized, double blind, placebo-controlled trial involving 497 multigravid pregnant women from a rural area of The Gambia. Women were randomly allocated to receive either oral iron (60mg elemental iron per day) or placebo. At 36 weeks of pregnancy, women who had received oral iron during pregnancy had higher mean haemoglobin, packed cell volume, plasma iron and ferritin levels than did women who received placebo. Iron supplementation of pregnant women with the AA haemoglobin genotype also resulted in increases in the packed cell volume (PCV) and haemoglobin level measured after delivery, and in the birth weight of the infant. However, in AS women PCV and haemoglobin level at delivery were lower in the supplemented group and supplementation was also associated with reduced birth weights. In malaria endemic areas, pregnant women with the haemoglobin genotype AS may not benefit from iron supplementation during pregnancy.