Time-dependent density functional theory (TDDFT) is combined with the multilayer fragment molecular orbital (FMO) method. The excitation energies of the system are estimated from those of its small active part, whereas the remaining part is described by its electron density distribution and the corresponding Coulomb field. The efficiency of this approach is illustrated on the lowest excitations of several solvated systems and phenylalanine-(alanine)(n). The full TDDFT excitation energies calculated are reproduced within 0.01 eV with LC-BLYP and the 6-31G* basis set. (C) 2007 Elsevier B.V. All rights reserved.