Altered 5 alpha-dihydrotestosterone (DHT) metabolism and stromal-epithelial cell interactions are two factors hypothesized to explain the development of benign prostatic hyperplasia (BPH). Furthermore, the development of BPH is clearly age dependent. Therefore, we studied the age-dependent alteration of 5 alpha-reductase, the enzyme that catalyzes the irreversible conversion of testosterone to DHT in epithelium and stroma of the human prostate. For this purpose kinetic parameters [Km Vmax] of 5 alpha-reductase were determined separately in epithelium and stroma of normal prostatic tissue (NPR) from 5 and BPH tissue from 20 men, and the results were correlated with the age of the donors (15-86 yr). The mean Km in epithelium [NPR, 14.3 +/- 1.8 (+/- SE); BPH, 29.5 +/- 2.7 nmol/L] was significantly (P less than 0.0001) lower than that in stroma (NPR, 78.4 +/- 8.5; BPH, 185.8 +/- 13.6 nmol/L). The mean Vmax in epithelium [NPR, 23.8 +/- 3.9 (+/- SE); BPH, 27.9 +/- 3.0 pmol/mg protein.h] was significantly (P less than 0.0001) lower than that in stroma (NPR, 68.3 +/- 4.4; BPH, 173.8 +/- 12.2 pmol/mg protein.h). The DHT-forming index (Vmax/Km) in NPR epithelium [1.6 +/- 0.2 (+/- SE)] was significantly (P less than 0.01) higher than that in NPR stroma (0.9 +/- 0.1), while in BPH the DHT-forming index was nearly identical in epithelium (1.1 +/- 0.1) and stroma (1.0 +/- 0.1). The Km values in epithelium and stroma both correlated positively (P less than 0.01) with age, but the Vmax values correlated positively with age (P less than 0.0001) only in stroma. The DHT-forming index decreased significantly with age in epithelium (P less than 0.01), but remained constant in stroma. These results indicate that there is a nonuniform age-dependent alteration of Km and Vmax in epithelium and stroma of the human prostate independent of the presence of BPH, which might have an impact on the conversion rate of testosterone to DHT with advancing age.