The present study was undertaken to elucidate the effects of ketanserin and trichlormethiazide on blood pressure in stroke-prone spontaneously hypertensive rats (SHRSP). Oral ketanserin and trichlormethiazide were administered to separate groups for 4 weeks. Combined ketanserin and trichlormethiazide was also administered and the effects observed. 1) In both ketanserin and trichlormethiazide administered groups, significant antihypertensive actions were observed as compared with the non-treated SHRSP. 2) In the ketanserin administered group, a significant increase in water drinking activity was observed, accompanied with an increased urinary volume. 3) In the trichlormethiazide administered group, urinary sodium excretion decreased significantly, accompanied with an increased urinary norepinephrine excretion. 4) Combined administration of ketanserin and trichlormethiazide enhanced the decreases in blood pressure which were produced by single administration of either ketanserin or trichlormethiazide. Moreover, both the increasing tendency in the urinary sodium excretion and the decreasing tendency in the urinary norepinephrine excretion occurred after the combined administration in SHRSP. These findings suggest that ketanserin produces an antihypertensive effect and may act prophylactically for thiazide-induced renal impairment in SHRSP.