The disease risk indicator plasma total homocysteine (tHcy) is influenced by genetic and environmental factors, including folate and vitamin B12 status. Little is known about the determinants of tHcy in rural West Africa. We explored the hypothesis that tHcy in rural Gambian adults might vary between the sexes and physiological groups, an/r with folate and vitamin B12 status. Comparisons were made with a British national survey. Non-pregnant Gambian women (n 158) had tHcy concentrations (geometric mean 9·0μmo/) similar to those of non-pregnant UK women (n 449; 9·4μmo/), whereas pregnant Gambian women (n 12) had significantly lower values (6·2μmo/). Gambian men (n 22) had significantly higher values (14·7μmo/) than British men (n 354; 10·8μmo/). Gambian lactating women and British men and women exhibited significant inverse relationships between loge(tHcy) and folate status; however, only the British subjects exhibited significant inverse relationships between loge(tHcy) and vitamin B12 status. In the British sample, and in Gambian lactating women, folate and vitamin B12 status variations together accounted for 20–25% of the variation in loge(tHcy). Within the UK, black-skinned adults had folate and tHcy levels similar to those of their white-skinned counterparts, but significantly higher vitamin B12 values. We conclude that, whereas folate and vitamin B12 status are similar between British and rural Gambian populations, tHcy is higher in Gambian men and lower in pregnant Gambian women, and that serum vitamin B12 values appear to be higher in black-skinned than white-skinned British subjects. Possible reasons are discussed.