Twenty new alkaloids, of which 13 are new natural products, have been discovered in Pachycereus weberi by tandem mass spectrometry using a mass-analyzed ion kinetic energy spectrometer. These observations have been confirmed by chromatography and, in many cases, by simple synthetic interconversions from known alkaloids. Particularly significant is the discovery of several alkaloids having the same molecular formula. Isomer distinctions such as these, which are difficult to make on pure compounds by mass spectrometry, were made by utilizing daughter spectra recorded successively during the evaporation of the material from the probe and/or from spectra recorded on different types of plant extracts. This study suggests that many natural materials may contain trace amounts of compounds of potential biomedical or synthetic interest and, in particular, that the number of known alkaloids might be greatly increased by experiments of this type. This study takes as its aim the discovery of new natural products in a complex matrix. Pachycereus weberi, commonly called candelabro and the largest of all columnar cacti, is native to Puebla and Oxaca provinces, Mexico (1-3). Prior to studies by tandem mass spectrometry (MS/MS), nine simple isoquinoline alkaloids were known to occur in the plant (4,5).