To prove whether the interaction between insertion/deletion (I/D) angiotensin I converting enzyme (ACE) and M235T angiotensinogen (AGT) gene polymorphic alleles could contribute to causing essential hypertension, we examined subjects from the Czech Republic (365 Caucasians total; 202 normotensives and 163 hypertensives). Subjects were genotyped for insertion/deletion polymorphism of ACE (I/D ACE, intron 16) and for M235T polymorphism of angiotensinogen gene (AGT, exon 2) by means of the polymerase chain reaction (PCR) method. The case-control approach was used. Fisher's exact test followed by Holmes's test to overcome the problem of multiple comparisons were used for the statistical analysis of data. No association of single gene allelic variants with essential hypertension was found in our population. Having compared only double homozygote combinations, the association of the DDMM genotype with essential hypertension was proven (P = 0.0081). To the contrary, IITT (P = 0.0086) was found more frequently in normotensive subjects. We conclude that the interaction of the I/D ACE and M235T AGT polymorphic alleles can contribute to essential hypertension, despite the absence of single gene associations with the condition.