The objectives of this work were to: (1) Determine if prostate and penile tissue levels of endothelin-1 (ET-1) are increased in a rat following pelvic irradiation. (2) Determine if an ETa receptor antagonist (BQ-123) potentiates erectile function in these irradiated animals. Rats were divided into three study groups: control, 1000 cGy and 2000 cGy. The experimental groups received a single dose of radiation to the pelvic region. A time course was established to measure the effects of irradiation on prostate and penile tissue levels of endothelin-1 (ET-1)-like immunoreactivity. The effect of intracavernous injection of BQ-123 (25 m mga30 m ml) was evaluated by measuring intracavernous pressure (ICP) following cavernous nerve electrical ®eld stimulation. In the 2000 cGy group, a signi®cant rise in ET-1-like immunoreactivity tissue levels was observed at 20 days. A signi®cant decrease in ICP was recorded in the 1000 and 2000 cGy irradiated rats compared to the control group. Only the 2000 cGy group had a signi®cant improvement in erectile function following BQ-123 administration. A signi®cant improvement was observed 20 min postadministration, lasted 90 min, and was back to pre-administered levels at 120 min. The conclusion made was that radiation-induced impotence in irradiated rats is associated with an increased production of ET-1. Preliminary results are suggestive that ETa receptor antagonist may be of use to reverse such radiation-induced impotence in these irradiated animals.