alpha-Naphthoflavone (ANF; 7,8-benzoflavone) is a potent competitive inhibitor of human aromatase cytochrome P-450 (J.T. Kellis, Jr. and L.E. Vickery, Science 225, 1032 (1984)). The authors have further investigated inhibition of aromatase by several derivatives of ANF. Using human placental microsomes and 40nM and androstenedione as substrate, the compounds tested and their I sub 50 values were: ANF, 0.07 microM; 2-(2-naphthyl)-4H-naphtho 1,2b pyran-4-one, 1.0 microM; 7,8-benzoisoflavone,identical with 100 microM; and 2-phenyl-4Hnaphtho 1,2b furan, > 100 microM. These findings show the necessity of the keto group of ANF in its binding to the enzyme and the importance of size and position of substitution of the exocyclic phenyl ring. (Copyright (C) Pergamon Journals, Ltd.)