The effect of gonadectomy on the antihypertensive action of pindolol in male spontaneously hypertensive rats (SHR) was investigated. And we also examined the relationship between the antihypertensive effect of this drug and the renal prostaglandin E₂ (PGE₂) level. In gonadectomized SHR, the reduction of blood pressure was not observed by the oral administration of pindolol, although the drug exhibited a marked antihypertensive activity in sham operated SHR. Urinary PGE₂ in sham operated SHR was increased following the administration of pindolol, but not in gonadectomized SHR. Similar results were obtained in the experiments using Wistar rats. The PG synthesis inhibition induced by indomethacin suppressed the antihypertensive action of pindolol. Results in the present study suggest that renal PGs, particularly PGE₂, are involved in the antihypertensive mechanism of pindolol, and that male gonad takes part in the regulation of the stimulation of the renal PGE₂ producing system induced by pindolol.