Electrospray ionization mass spectrometry (ESI-MS) precisely measures molecular masses without disrupting noncovalent protein interactions, and so provides a powerful tool for studying protein complexes. In this issue ( p.1214), Naylor and colleagues take the method a step further, using it to analyze the effect of ligands on heterodimerization of full-length vitamin D and retinoid X receptors, and their binding to specific DNA sequences.