In order to evaluate their potential for molecular surface analysis, we applied monoatomic (Ga, Cs, An, Bi) as well as polyatomic (SF5, Au-n, Bi-n, C-60) primary ions to a series of organic samples. For the model system Irganox 1010 on LDPE we determined the secondary ion yield, the disappearance cross section and the resulting ion formation efficiency as a function of the primary ion energy. As a general result the efficiency is improved with the mass of the monoatomic primary ion. A further increase is obtained by the use of polyatomic primary ions. According to this, highest efficiencies are obtained for C-60, the lowest for Ga. Additionally, molecular imaging was performed on real world samples (electronic components, pharmaceuticals): for this a cluster LMIS operated with Ga, AuGe or Bi was applied. The results reveal the potential of cluster SIMS to overcome existing limitations and to establish TOF-SIMS for new applications in the fields of polymers, biology and medicine. (C) 2004 Elsevier B.V. All rights reserved.