Using the results of molecular dynamics (MD) simulations, we discuss the question of whether the observed difference in mass limits in secondary ion mass spectrometry (SIMS) and matrix assisted laser desorption ionization (MALDI) are inherently related to the underlying physics of ejection or rather insufficient experimentation. The simulations show clearly that the physics of large molecule emission in SIMS and MALDI is very different. Consequently, we conclude that larger molecules can be ejected in MALDI than in SIMS. (C) 2002 Elsevier Science B.V. All rights reserved.