During a fifteen-month period, 15 patients with progressive adenocarcinoma of the prostate (CaP) were treated with transrectal microwave hyperthermia (TRHT). There were 5 Stage T4 and 11 Stage T3 patients including 6 patients with skeletal metastases. Nine of the patients had severe and 6 had moderately severe signs and symptoms of CaP TRHT was given six times at 2,450 MHz with temperature controlled at 43.5-degrees for thirty minutes. Cell-mediated immunity tests were performed before TRHT and at two, four, and six months post-therapy. The results of these tests were compared with those of 15 patients with benign prostatic hyperplasia (BPH) treated with the same TRHT and with 30 untreated normal volunteers. TRHT was well tolerated with mild acute toxicity noted in 3 patients (20 %). Of the 15 patients treated, 2 (13 %) showed scintigraphic evidence of regression of bone metastases. Five patients survived more than five years since treatment, and in 3 patients there was no evidence of CaP. A decrease of marked or moderate degree in signs and symptoms of CaP was noted in 8 patients (53 %). The results of cell-mediated immunity tests were of interest. The 15 CaP patients prior to TRHT had lower OKT4/OKT8 ratio, lower PHA transformation index, and lower Con-A induced T-cell suppressor activity as compared with the 15 BPH patients and 30 healthy volunteers, who had normal immune parameters (p < 0.01). Following TRHT there was a significant increase in the monitored immune parameters noted in the 15 CaP patients (p < 0.01). This immune stimulation peaked at two months and gradually decreased to near pretreatment levels at six months. In the 15 BPH patients post-TRHT changes in immune tests were less apparent. The results of this small study, if confirmed, could be of clinical importance in patients with advanced prostate cancer.