A recent cross-sectional study of HTs in Salt Lake City and Paris has reported a significant association of a T704-->C (Met235-->Thr) variant in exon 2 of the angiotensinogen gene (AGT) with essential hypertension (HT). The present study used a new, direct PCR technique to detect this variant in 92 Caucasians with severe hypertension (HT) and two HT parents and 94 normotensive (NT) controls. Although frequency of the variant in HTs (0.42) was higher than in NTs (0.39), the difference was not significant (chi 2 = 0.24; P = 0.63). Plasma angiotensinogen showed a weak, nonsignificant relationship with AGT genotype in females and no genotypic relationship was apparent for blood pressure. Thus, if the Met235-->Thr variant of AGT is involved in essential HT, then its contribution may be, at best, much weaker in other HT groups.