In the present study, homocysteine (Hcy) and vitamin B status were determined in healthy subjects living in two opposite regions of the Ivory Coast. Fifty-six subjects from a coastal region (Bodou) having a fish-based diet and 56 subjects from a mountainous area (Glanle) having a vegetarian diet were tested to sample Hcy, folate, vitamin B12, creatinine, and lipid levels, as well as inflammation and nutritional parameters. An increased prevalence of Hcy >/=15micromol/L was observed, reaching 60 % of all subjects. The Bodou group exhibited significantly higher Hcy levels than the Glanle group [20.1 (9.7 - 41.4) vs. 13.6 (5.5 - 48.7) micromol/L, p<0.0001], despite higher vitamin B12 levels [593 (163 - 1860) vs. 234 (83 - 585) pg/mL, p<0.0001]. Although folate levels were lower in subjects from Bodou compared to Glanle [3.2 (2.0 - 7.3) vs. 6.0 (1.9 - 18.2) ng/mL, p<0.0001], there was no significant relationship with Hcy levels in any groups. Interestingly, there were significantly higher creatinine levels in subjects from Bodou compared to Glanle and a significant positive relationship with Hcy levels was evident in each group. In conclusion, Hcy levels in an Ivorian population having a fish-based diet appeared significantly higher compared to subjects having a vegetarian diet. However, folate and vitamin B12 status did not emerge as the major determinants of this difference; a stronger relationship was observed with creatinine levels.