Electrospray ionization mass spectrometry (ESI-MS) is a powerful tool for examining the charge of proteins in solution. The charge can be manipulated through choice of solvent and pH. Furthermore, solution-accessible, protonated lysine side chains can be specifically tagged with 18-crown-6 ether to form noncovalent adducts. Chemical derivatization of a protein in this fashion followed by "soft" ionization can provide a wealth of specific information regarding side chain identity, location, and surface chemistry. A variety of proteins are examined with ESI-MS under a range of conditions in this self-guided experiment, and the results are compared with those predicted from structural information available in the protein data bank.