Objective:To determine whether a microsatellite polymorphism of the insulin receptor gene (INSR) is associated with essential hypertension, as has been demonstrated previously for anRsalrestriction fragment length polymorphism (RFLP), and to examine blood pressure and plasma lipid profiles in relation to genotype.Design and methods:The study involved 75 Caucasian, non-diabetic hypertensive patients whose parents were both hypertensive, and 75 age-matched normotensive subjects whose parents were each normotensive after the age of 50 years. Genotypes for the microsatellite polymorphism were determined for each subject using leucocyte DNA and a polymerase chain reaction method. Other parameters, including pretreatment blood pressure, body mass index and plasma lipids, were also determined.Results:Comparison of microsatellite data for the eight genotypes and four alleles that were detected showed no significant difference by χ2analysis, either between the hypertensive and normotensive groups, or between obese and non-obese subgroups of hypertensives. This is in contrast to the significantly higher frequency seen for theR1- allele of anRsalRFLP ofINSR: 0.71 in the hypertensive group compared with 0.56 in the normotensive group.R1- allele frequency was elevated in all age groups of hypertensives and did not differ between obese and non-obese subgroups. The non-obese hypertensives also had different plasma lipid profiles according to genotypes of the RFLP, with higher total and low-density lipoprotein-cholesterol in patients having the hypertension-associatedR1- allele of the intron 9 polymorphism. Moreover, systolic blood pressure was significantly greater in patients carrying theR1- allele and aged ≤60 years.Conclusions:The present study allows definition of the hypertension-associated variants ofINSRas those which are in linkage disequilibrium with a (CA)-repeat insertion polymorphism in intron 9 of the large, 22 exon, >120-kb gene, but not those associated with a polymorphism in the second intron.