The spontaneously hypertensive rat and the Dahl salt-sensitive rat are the most widely studied genetic models of hypertension. Many investigators have attempted to study the pathogenesis of hypertension by comparing these strains with their respective normotensive "controls," the Wistar-Kyoto rat and the Dahl salt-resistant rat. However, the genetic relation between each of these hypertensive strains and its corresponding normotensive control has never been clearly defined. Based on an analysis of DNA "fingerprint" patterns generated with six multilocus probes, we found that the spontaneously hypertensive rat (Charles River Laboratories, Inc.) is genetically quite different from its normotensive Wistar-Kyoto control: these strains only share approximately 50% of their DNA fingerprint bands in common. The inbred Dahl salt-sensitive rat (SS/Jr strain) (Harlan Sprague Dawley, Inc.) and the Dahl salt-resistant rat (SR/Jr strain) share approximately 80% of their DNA fingerprint bands in common. To the extent that the genes identified by DNA fingerprint analysis are representative of loci dispersed throughout the rodent genome, the current findings provide evidence of extensive genetic polymorphism between these commonly used hypertensive strains and their corresponding normotensive controls, particularly in the spontaneously hypertensive rat model. These findings, together with the fact that an enormous number of biochemical and physiological differences have been reported between these hypertensive and normotensive strains, suggest that continued comparison of spontaneously hypertensive rats with Wistar-Kyoto rats or Dahl salt-sensitive with salt-resistant rats will have limited value for investigating the pathogenesis of hypertension.