The present experiments were undertaken to elucidate the effect of long-term administration of clonidine and its cessation on blood pressure, heart rate and sympathetic nerve activity in spontaneously hypertensive rats (SHR). A five week administration of clonidine (approximately 3ç0 micrograms/kg/day) produced a decrease in body weight and food intake. During clonidine administration, blood pressure showed a significant decrease. It was noted that blood pressure recovered rapidly toward the control level within 24 hours after clonidine cessation. No significant changes in heart rate were observed during clonidine administration and after its cessation. Clonidine administration produced a significant decrease in urinary norepinephrine excretion. After clonidine cessation, decrease in urinary norepinephrine excretion during clonidine administration recovered fully to the control level. No significant changes in plasma norepinephrine content were observed during clonidine administration. When the drug was discontinued, plasma norepinephrine content rose significantly as compared with that in control. The renal sympathetic nerve discharges during clonidine administration showed a significant decrease. It was noted that the renal sympathetic nerve discharges after clonidine cessation recovered fully to the control level. These findings suggest that the decrease in the peripheral sympathetic activity is associated with clonidine induced hypotension in SHR. It is also suggested that the increase in the peripheral sympathetic activity induced by clonidine cessation is responsible for the recovery of blood pressure to the control level in SHR.