These experiments represent work toward the development of an efficient screening protocol for noncovalent complex formation by guanidinium- and phosphonate-containing amino acid molecules (e.g., arginine (Arg) and phospholeucine (pLeu)) with electrospray ionization mass spectrometry (ESI-MS). Mass spectra, acquired with an optimized ESI-MS method, reveal the formation of multiple high order adducts in the positive and negative ionization modes. Relative transmission factors, defined based on the relationship between measured ion intensities and the initial concentration of each component in an equimolar mixture, for all free and bound ion forms are determined for qualitative comparison of the effects of covalent modification of amino acid-type analytes (N-acetylation of Arg and pLeu and C-amidation of Arg) on noncovalent interactions. Correlation of measured mass spectra with solution-phase equilibria are tested through quantitative mass spectrometric titration experiments. Poor correlation with the ascribed model indicates the likelihood that processes other than solution-phase equilibria are responsible for the majority of the observed ionic complexes. For quantitative measurement of binding in the gas phase, collision-activated dissociation (CAD) is used to determine half-dissociation thresholds of parent ions (E 1 / 2 ). These values provide a measure of relative stability of the ionic complexes in the absence of solvent. Results from relative transmission factors and E 1 / 2 measurements show a high degree of variation for ionic complex response based on the covalent modifications of the amino acids which form the complex. Overall, the combination of these approaches offers a means for monitoring and selecting (i.e., screening) systems that interact favorably through a combination of ionic and hydrogen-bonding interactions. Favorable cases can then be isolated for further study, preferably by CAD methods.