A constant infusion of (3)H-testosterone and (14)C-androstenedione was administered to four human subjects, two males and two females, until the concentrations of radioactive testosterone and androstenedione in systemic plasma became constant. At that time the concentrations of radioactive testosterone and androstenedione in hepatic vein plasma were determined. Splanchnic extraction of testosterone and androstenedione and the contribution of the splanchnic system to the blood interconversion of testosterone and androstenedione were calculated. Androstenedione is extracted by the splanchnic system more efficiently than testosterone since 82.3% of androstenedione and 44% of testosterone were removed from the plasma after one passage. The fraction of testosterone entering the splanchnic system that is transferred to blood androstenedione was 0.011 and the maximum possible transfer due to recirculation was 0.026. This was 28% of the total blood transfer from testosterone to androstenedione. The fraction of androstenedione entering the splanchnic system that is transferred to blood testosterone after one passage was 0.005, whereas the maximum possible transfer in this system was 0.006. This represented only 16% of the total transfer from androstenedione to testosterone. Therefore, a large fraction of the interconversion of testosterone and androstenedione in vivo occurs outside the splanchnic system.