The association between restriction fragment length polymorphism (RFLP) in the 3'-untranslated region of the dopamine /9-hydroxlase (DBH) gene and essential hypertension, and the relationship between this RFLP and plasma DBH activity were investigated. A 322 by segment of the 3'-untranslated region of the human DBH gene was amplified by polymerase chain reaction (PCR). The restriction enzyme SphI cleaved the 322 by PCR product into 201 and 121 by fragments for that allele which contained the SphI cutting site. This allele was designated S. The allele that lacked the SphI restriction site was designated L. Plasma DBH activity was determined by a spectrophotometric method. For this polymorphic restriction site, the frequency of the minor allele of the polymorphism was similar in the hypertensive and normotensive groups (0.39 vs. 0.35, respectively). In the normotensive group, there was a significant (p < 0.01) relationship between plasma DBH activities and genotypes: 65 ± 24, 55 ± 20 and 45 ± 14 IU/i for homozygotes (LL), heterozygotes (LS) and homozygotes (SS), respectively. In the hypertensive group, no significant relationship was observed. These results demonstrate that a SphI RFLP in the 3'-untranslated region of the DBH gene is not associated with essential hypertension in the group studied. However, in only normotensive subjects, this RFLP may be responsible in part for the variance of plasma DBH activity. (Hypertens Res 1994; 17: 49-53)