Deficiencies in Cu, Se, and Zn impair one or more biochemical functions, and excess are associated with toxicity. Baseline studies on the Ghanaian population are scanty. The study was undertaken to determine whether significant rural/urban differences in the serum levels of Cu, Se, and Zn did exist. Forty males/60 females from rural and 50 males/50 females from urban Ghanaian communities were sampled. Serum Cu, Se, and Zn were determined using flame atomic absorption spectrometry. Cu level for rural and urban subjects was 997 +/- 333 and 979 +/- 290 microg/L, respectively (p = 0.68). However, Cu levels were significantly higher in the rural females (1,063 +/- 367 microg/L) than the rural males (898 +/- 249 microg/L; p = 0.0085). Se levels for rural/urban subjects were 97 +/- 36 and 87 +/- 31 microg/L, respectively (p = 0.03). Zn levels in the rural/urban subjects were 312 +/- 218 and 150 +/- 102 microg/L, respectively (p = 0.002). Additionally, Zn was significantly higher in rural females (428 +/- 204 microg/L) than the urban females (166 +/- 103 microg/L; p = 0.0002). Finally, Zn was significantly higher in rural females (428 +/- 204 microg/L) than males (172 +/- 116 microg/L; p = 0.0028). In conclusion, Cu, Se, and Zn were higher in the rural group compared to the urban group, and the generally low Zn levels were confirmed in another cohort follow-up study.