The splanchnic extraction and interconversion of testosterone and dihydrotestosterone (DHT) were studied in 7 healthy men (ages 29-46 years) undergoing cardiac catheterization. During a constant infusion of [1,2-3H]testosterone and [4-14C]DHT, the arterial and hepatic vein blood samples were taken and radioactive and non-radioactive testosterone and DHT were determined. Metabolic clearance rate (MCR), splanchnic extraction (SE), splanchnic clearance (SC), extrasplanchnic clearance (ESC), transfer constant in blood (T-DHT rhoBB) and transfer constant across the liver (T-DHT rhoSB) were calculated. The MCRT was 952 +- 172 (mean +- SD) 1/day and MCRDHT was 764 +/- 67 1/day in agreement with data from non-catheterized subjects. SET was 68.8 +/- 7.1% (mean +/- SD) and SEDHT was 37.6 +/- 5.9%. SET was significantly greater than SEDHT (P less than 0.001). The calculated SCT and ESCT were 638 +/- 112 (mean +/- SD) 1/day and 314 +/- 190 1/day, respectively. SCDHT and ESCDHT were 343 +/- 95 (mean +/-SD) 1/day and 421 +/-105 1/day, suggesting that a major fraction of testosterone is metabolized in the splanchnic organs and a higher fraction of DHT is metabolized in extrasplanchnic organs. In the interconversion study, overall conversion of testosterone to DHT in blood (T-DHT rhoBB) was 4.0 +/- 0.6% (mean +/- SD). No evidence for a net appearance of DHT by either mass or specific activity analysis in hepatic vein blood was observed in any infusion leading to the conclusion that the overall contribution of testosterone to circulating DHT from the liver (T-DHTrhoSB) was undetectable. This work indicates that conversion of testosterone to DHT occurs entirely in extrasplanchnic tissue in man.