4-Substituted N-(1,1-dimethylethyl)-3-oxo-4-androstene-17 beta-carboxamides with the hydroxy (OH) 3d, mercapto (SH) 3e, chloro (Cl) 3f, and bromo (Br) 3g substituents at the 4-position were prepared in a two-step sequence with overall yields of 21%, 27%, 41%, and 37%, respectively. Compounds 3d-g showed weak inhibitory activity on human type I 5 alpha-reductase (IC50 > or = 700 nM) while they had intermediate inhibitory activity on human type II 5 alpha-reductase at IC50S of 172, 437, 192, and 387 nM, respectively. In androgen-sensitive Shionogi cells, the inhibition of dihydrotestosterone (DHT) stimulatory action on the proliferation of the androgen-sensitive cancer cells by all four compounds was high at IC50S of 170-279 nM compared with 117 nM for hydroxyflutamide. The present data show compounds having both moderate inhibition of human type II 5 alpha-reductase activity and relatively potent antiandrogenic action, two beneficial characteristics in the therapy of androgenic-sensitive diseases.