The energy dependence of fragmentation in a collision cell was measured for 2400 protonated peptide ions derived from the digestion of 24 proteins. The collision voltage at which the sum of the fragment ion abundances was equal to the remaining parent ion (V(1/2)) was the principal measure of fragmentation effectiveness. Each class of peptides was characterized by a linear relation between V(1/2) and m/z whose slope depended on the peptide class and, with little adjustment, intersected the origin. Peptide ions where the number of protons is no greater than the number of arginine residues show the greatest slope, V(1/2)/(m/z) = 0.0472 (all slopes in units of V Da(-1) e). For peptides where the number of protons is greater than the number of arginines, but not greater than the total number of basic residues, the slope decreases to 0.0414 for singly charged ions, 0.0382 for doubly charged, 0.0346 for triply charged, and 0.0308 for more highly charged ions. With one mobile proton, the slope is about 0.029 for singly and doubly charged ions and slightly lower for more highly charged ions. With two or more mobile protons the slope is 0.0207. By removing m/z dependence, the deviation of V(1/2) from a line provides a relative measure of the ease of fragmentation of an ion in each class. This information can guide the selection of optimal conditions for tandem mass spectrometry studies in collision cells for selected peptide ions as well as aid in comparing the reactivity of ions differing in m/z and charge state.