The transgenic rat line TGR(mREN2)27 has been previously shown to develop severe hypertension as a consequence of over-expression of the mouse Ren-2 renin gene. The heterozygote cross HanRen2/Edin - was found to develop malignant phase hypertension within a relatively narrow age range. Seventy-three percent of male and 52% of female HanRen2/Edin - developed malignant hypertension. In contrast, other heterozygote crosses HanRen2/Han - and HanRen2/Lew - had an incidence in males of 18% and 0% and in females of 4% and 0% respectively. Telemetry was used to record blood pressure continuously in unrestrained conscious rats and demonstrated an accelerated rise in blood pressure in rats with clinical features of malignant phase hypertension. Histopathology showed fibrinoid necrosis and myo-intimal proliferation of afferent arterioles and small renal arteries. An associated deterioration in renal function occurred with a rise in plasma urea and creatinine. TGR(mREN2)27 normally have a suppressed renal renin-angiotensin system but in malignant phase affected animals had a significant elevation of plasma renin, angiotensin II and aldosterone. Immunohistochemistry demonstrated increased renin at the site of the afferent arterioles near the vascular poles of glomeruli. Blood films demonstrated a microangiopathic haemolytic anaemia. A genetic basis for the differing incidence of malignant phase between the three heterozygote crosses were further supported by the results of an analytical cross set up to segregate Edinburgh Sprague-Dawley alleles. Results suggested that malignant phase hypertension complicated benign hypertension due to the effects of one or possibly two genetic loci. In conclusion, this is a representative model showing many of the characteristics of malignant phase hypertension in humans. The differing incidence between transgenic Ren-2 crosses appeared to be consequence of genetic factor(s). This may therefore by another example of a genetic pre-disposition to develop target organ damage from hypertension.