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Analysis of the effect of naloxone (0.4 mg iv.) on clonidine hypotension in 80 patients with essential hypertension revealed that two groups could be separated. In the responding group (43 pts) naloxone increased blood pressure and heart rate in clonidine-treated patients while in the non-responding group (37 pts) it has no such effect. Patients in the responding group had higher cardiac output, stroke volume, plasma renin activity, plasma adrenaline and beta-endorphin levels and lower total peripheral resistance, shorter history of hypertension and lesser body weight than those in the non-responding group. The pressor effect of naloxone in four responding patients treated with clonidine for 29 months tended to be smaller compared to the response obtained after a 3-day clonidine therapy. Results favour the hypothesis of the existence of two (responding, non-responding) groups of patients with essential hypertension. Further work will clarify whether these groups represent different pathogenesis or they indicate only a different stage of hypertension.