CYP3A5 (cytochrome P450, family 3, subfamily A, polypeptide 5) expression stimulates the sodium retentive actions of the mineralocorticoid receptor causative of hypertension, probably by means of its ability to substantially increase the level of 6β-hydroxylase activity. Most Black individuals are functional CYP3A5 expressers, and this is a candidate gene for the high incidence of hypertension in Black populations. The study investigates whether CYP3A5 expression results in higher blood pressure in a Ghanaian population. Real-time PCR was used to genotype 898 DNA samples for the CYP3A5*3 and CYP3A5*6 single-nucleotide polymorphisms with technically adequate genotyping for 881 samples. Of these, 803 were genetic CYP3A5 expressers, 44 nonexpressers and 34 uncertain (CYP3A5*3/*6). Although there was a trend in the proportion of hypertensive individuals as CYP3A5 expression decreased, using a two-sided t-test, no statistically significant relationship was established between systolic or diastolic pressure and CYP3A5*3 or CYP3A5*6 genotypes, or their haplotypes (Systolic confidence interval: -8.44 to -7.70, P=0.93, Diastolic confidence interval: -4.89 to 4.85, P=0.99). We conclude, therefore, that there is either no association between CYP3A5 expression and blood pressure or, if there is a relationship, the strength of the association is very small.