Transition moment directions of chromophores are critical for predicting CD and absorption spectra of biological macromolecules. Single-crystal polarized reflection spectra of a primary amide (propionamide, PrN) and a secondary amide (N-acetylglycine, NAG) were recently analyzed, yielding transition moment directions for the first (NV1) and second (NV2) pi pi* transitions (Clark, L. J. Am. Chem. Sac. 1995, 117, 7974). In terms of the angle theta, measured from the C=O bond with the C-N bond at positive theta, the directions for the NV1 transitions are -37 degrees for PrN and -55 degrees for NAG. INDO/S MO calculations on the isolated molecules give NV1 transition moment directions of -25 degrees and -36 degrees for PrN and NAG, respectively. When the mixing of excited states due to the crystal field and the exciton effect are considered, the calculated angles are -35 degrees and -42 degrees, respectively. For the NV2 transitions, the angles (experiment for crystal, theory for free molecule, theory for molecule in crystal) are 46, 59, 49 degrees for PrN and 61, 53, 55 degrees for NAG. The present results are compared with recent ab initio results. It is proposed that the best results may be obtained by combining ab initio transition moment directions for the isolated molecule with the gas-to-crystal shift calculated by the present semiempirical method. Simplified charge models have been developed that give results for crystals of NAG essentially equivalent to those obtained with the detailed charge model. The method used in the prediction of the CD and absorption spectra of polypeptides for calculating the mixing of excited states under the influence of a static field was tested on crystals of NAG with satisfactory results. Calculations for an amide group in the middle of a 21-peptide alpha-helix give theta = -42 degrees for the NV1 transition.