Pregnanedione (5β-pregnane, 3,20-dione), pregnanolone (3β-hydroxy-5β-pregnan-20-one), and epipregnanolone (3α-hydroxy-5β-pregnan-20-one) result from the 5β-reduction of progesterone [4-pregnene, 3-20-dione (P)]. These P metabolites induce anesthesia and smooth muscle relaxation (nongenomic actions). In the present study, geometries and electronic structure of these steroids were assessed by ab initio calculations using the 6-31G* basis set. Consequently, bond distances, valence angles, and dihedral angles were measured. In addition total energy, frontier orbitals, i.e., highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), dipole moment, and electrostatic potentials were calculated. Total energy was higher for P, followed by pregnanedione. Pregnanolones, the hydroxylated progestins, showed the lower energies. Concerning frontier orbitals, P showed the highest HOMO energy and the lowest LUMO energy. Pregnanedione showed lower HOMO and LUMO energy values than pregnanolone and epipregnanolone. P showed both HOMO and LUMO located at the A ring, including the π bond at C4, C5, and the carbonyl at C3. The HOMO in pregnanedione was included mostly in the A ring and the C3 carbonyl group, while the LUMO was shared by the carbonyl groups at C3 and C20. The frontier orbitals of pregnanolone and epipregnanolone were quite similar. The HOMO in both steroids included the B, C, and D rings and the carbonyl at C20. The LUMO was also similar in both pregnanolones including mostly the carbonyl at C20. The dipole moment was shorter for P and pregnanedione and directed toward the acetyl side chain at C17. Pregnanolone and epipregnanolone showed the dipole moment vector larger and directed toward the A ring. The electrostatic potentials were related mostly with the lone pairs of electrons from the oxygens. By the total energy and frontier orbitals energies of the hormones studied, it is concluded that the metabolism of progesterone toward its 5β-reduced metabolites might be rationalized from the theoretical chemistry point of view. Besides, the importance of the A/B ring cis configuration, dipole moment, and electrostatic potential are highlighted as possible improving elements of molecular interactions to explain the nongenomic biological action of 5β-reduced progestins. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 71: 433–440, 1999