Spontaneous development of malignant phase hypertension in TGR(mREN2)27 heterozygotes occurs as a consequence of crossing TGR(mREN2)27 homozygotes with Edinburgh Sprague-Dawley rats. Similarities to human malignant phase hypertension are seen with an accelerated rise in blood pressure, fibrinoid necrosis of renal afferent arterioles, renal failure and evidence of renin-angiotensin system activation. It appears that introduction of an additional genetic factor or factors into a monogenic model of hypertension results in malignant phase hypertension.