The potent synthetic androgen 7 alpha-methyl-19-nortestosterone (MENT) is resistant to 5 alpha-reductase but is a substrate for aromatase. It may therefore offer selective sparing of the prostate gland while supporting other androgen-dependent tissues. MENT acetate implants were administered for 24 wk to 16 hypogonadal men, randomly allocated to 1 or 2 implants (groups I and II, respectively; releasing approximately 400 microg/d x implant). Hemoglobin concentration and hematocrit were maintained during MENT treatment. Prostate volume fell in group I and to a small, but statistically nonsignificant, degree in group II; the level of prostate-specific antigen fell significantly in both. Lumbar spine bone mineral density decreased in both groups. Sexual behavior and erectile function declined in group I, but were maintained in group II. Thus, overall, one MENT implant appeared to provide subphysiological androgen replacement. The 2-implant dose of MENT was able to maintain most androgen-dependent functions, except bone mass, and there was evidence to support selective sparing of the prostate gland. These results demonstrate for the first time in humans the selectivity of MENT in tissues dependent on 5 alpha-reductase. In addition, our data are consistent with the importance of adequate estrogenicity as part of the necessary spectrum of activity of an androgen for replacement therapy in men.