The prospect of improved secondary ion yields for secondary ion mass spectrometry (SIMS) experiments drives innovation of new primary ion sources, instrumentation, and postionization techniques. An important factor affecting the detection sensitivity in molecular SIMS and other desorption techniques as well is believed to be the poor ionization probability of a sputtered molecule, a value which is often assumed to be as low as 10–5 but at present is basically unknown. In order to estimate how much headroom there is for future developments toward strategies aimed at enhancing the ionization probability, we study the protonation efficiency of sputtered guanine molecules for formation of [M + H]+ secondary ions using strong field laser postionization (LPI) to detect the corresponding neutral molecules. In order to allow a quantitative comparison of secondary ion and neutral yields, the postionization signal is corrected for undersampling of the principally detectable plume of sputtered neutral particles by t...