Microwave irradiation administered by transurethral transducer to the prostate permits focused hyperthermia with resultant tissue ablation; a coding system within the catheter allows urethral preservation. We evaluated the effect of microwave hyperthermia in 13 dogs receiving 48-79 min of focused irradiation (16-45 watts, intraprostatic temperature > 45 degrees C) delivered by a specially-designed transducer with an operator-controlled directional antenna (T3, Urologix Inc., Minneapolis, MN); one other dog had transducer placement without irradiation (sham control). After treatment, the dogs were in good health, voiding well without complications, and were sacrificed after 5-38 days. The prostate and vasa deferentia were removed, fixed in 10% formalin, grossly inspected, cut at 5 mm intervals, and serially sectioned with whole mount sections; representative sections of the adjacent rectum and distal bladder were also obtained. All cases were histologically evaluated with prostatic mapping without knowledge of treatment or time of sacrifice. In the acute phase (5-13 days), the prostate showed sharply circumscribed periurethral coagulative necrosis with hemorrhage; necrosis was also seen in the mucosa and bladder wall of those with transducers placed at the bladder neck. In the subacute phase (17 days), the hemorrhagic necrosis was resolving, often with cystically dilated urethra due to sloughed necrotic tissue; the urothelium was intact. By 24-38 days, the necrosis was in the late stages of resolution, with residual patchy acute and chronic inflammation at the periphery, and frequent persistence of megalourethra. In all cases, the prostatic capsule was intact, the urethral mucosa was preserved, and the vasa deferentia and rectum were normal except for two cases with mild fat necrosis. Microwave irradiation allows precisely localized thermal ablation of prostatic tissue and enlargement of the urethral bore without clinical complications in dogs, offering promise as a therapeutic alternative to surgery in select patients with symptomatic prostatic nodular hyperplasia.