Progressive elevation of the prostate specific antigen (PSA) level after radical prostatectomy for adenocarcinoma is generally considered as irrefutable evidence of recurrent tumor. We assessed the results of 62 biopsies of the vesicourethral anastomosis in 41 men who had 3 or more consecutive PSA levels of 0.4 ng./ml. or greater after radical prostatectomy and no evidence of metastatic disease. The median PSA at the time of the first biopsy was 2.2 ng./ml. (range 0.4 to 50). Histological confirmation of recurrent cancer was established after 1 biopsy procedure in 39% of the patients and after 1 or more biopsy procedures in 59%. Biopsy was positive in 78% of 23 patients with an abnormal digital rectal examination, 40% of 5 with an abnormal transrectal ultrasound only, and 23% of 13 with a normal digital rectal examination and ultrasound. Among the patients with and without biopsy proved tumor recurrence there were no significant differences between the pathological stage or histological grade of the primary tumors, the month after surgery of the first detectable PSA level, the PSA doubling time, the month after surgery of the positive biopsy or the last negative biopsy, and the PSA level at the time of the positive biopsy or the last negative biopsy. In 6 cases benign prostatic tissue only was recovered from 1 or more biopsy specimens. This experience demonstrates that in patients with a detectable PSA after radical prostatectomy recurrent cancer may be difficult to document by biopsy of the vesicourethral anastomosis.