Objectives. To evaluate biochemical outcome after definitive radiotherapy as a function of family history groupings. Methods. Biochemical freedom from disease for 920 men treated for prostate cancer with external beam radiation alone between March 1987 and December 1997 was compared according to hereditary/familiar history (PFH) and sporadic family history. To adjust for known predictors of biochemical outcome, 97 PFH patients were randomly matched 2:1 to 194 sporadic patients according to age, grade, pretreatment prostate-specific antigen level, and palpation stage and compared in terms of biochemical outcome. Cox multivariate regression analyses were also performed to identify independent predictors of outcome in the two patient populations. Results. In both patient populations, univariate analysis of biochemical outcome demonstrated no difference according to family history groupings. After adjusting for known predictors of biochemical outcome, multivariate analysis confirmed the nonsignificant univariate findings. Conclusions. No difference was found in this study between patients with a PFH (combined hereditary and familial) and patients with the sporadic form of prostate cancer. Recent published reports are conflicting and the question of whether a genetic change influencing prostate cancer causation is associated with factors altering treatment response should be addressed using a multi-institutional, carefully documented, prospective family history data collection and outcome analysis. (C) 1998, Elsevier Science Inc. All rights reserved.