During radiotherapy for prostate cancer, the ability to predict occult seminal vesicle invasion is important since irradiation of the entire seminal vesicles necessitates enlarging the radiation fields beyond what is usually used to irradiate the prostate gland alone. We analyzed the records of 302 patients with clinical Stage T1 or T2 adenocarcinoma of the prostate treated with radical surgery at Duke University Medical Center between 1970 and 1983. Univariate and multivariate analyses were used to examine the relationship between the risk of occult seminal vesicle involvement (defined herein as histologic involvement of the seminal vesicles not detected by physical or radiologic examination) and the following factors: histologic grade, age, clinical stage, and preoperative acid phosphatase. Among 249 patients with complete information, increasing histologic grade (p < 0.001) and clinical stage (p < 0.04) were found to be the strongest predictors of occult seminal vesicle invasion. Conversely, seminal vesicle invasion was very unusual in well-differentiated T1-T2 tumors (6%). This low risk group represented 28% (70/249) of this patient population. There appears to be a substantial subset of patients with well differentiated T1 or T2 tumors who are at very low risk for occult seminal vesicle involvement and in whom the seminal vesicles can be excluded from the target volume. The reduction in target volume may reduce normal tissue reactions, facilitate dose escalation, and possibly increase local control rates.