The authors tested the single and combined effects of nuclear and mitochondrial DNA genotypes on the phenotypes of systolic blood pressure (SBP) and weight, and their changes over 5 years in normotensive subjects living in Barbados. The nuclear genotypes were gender (Y chromosome), haptoglobin (HP), and group specific component (Gc). A mitochondrial genotype was chosen as a marker for maternal lineage. Baseline clinic SBP and weight (N=78), 24-hour SBP (N=28) were measured. Five years later, clinic SBP and weight were measured again in 28 participants. Male participants generally had higher pressures than female participants. The HP genotype was associated with 5 of the 8 SBP phenotypes. The haptoglobin-1 (HP1) allele was associated with higher clinic (P=.024) and evening SBP at baseline (P=.020). The effect of HP1 appears to be dominant. Haptoglobin-2 (HP2) was associated with the increase in weight over 5 years (P=.002). Group specific component (Gc) genotype was associated with 6 of the 8 SBP phenotypes. The Gc polymorphism 2 was associated with higher 24-hour SBP, sleep SBP (midnight-6 AM), afternoon SBP (noon-6 PM) and evening SBP (6 PM to midnight). Furthermore, we found a significant association between the haptoglobin/mt-DNA and Gc/mt-DNA polymorphisms with SBP between 6 PM and midnight (P=.009 and P=.011, respectively). The 5-year changes in SBP were significantly associated with the haptoglobin/mt-DNA and Gc/mt-DNA polymorphisms (P=.005 and P=.011, respectively). Multivariate analysis for genetic effects on change in weight and change in BP suggested the rise in BP, but was not suggestive of change in weight. Furthermore, multivariate analysis was associated with Gc, but not Haptoglobin genotype. In normotensive subjects of African descent living in Barbados, the increase in blood pressure with age is significantly influenced by both nuclear and mitochondrial genotypes that are more common in African derived populations.