Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry is becoming more widely used among the mass spectrometric techniques and has excellent figures of merit. Ion activation and fragmentation via sustained off-resonance irradiation (SORI) collision-induced dissociation (CID) is commonly used in FT-ICR. However, one of the limitations of SORI-CID is that only low-energy processes are typically observed in the product ion spectra. Here we present another option for performing CID in FT-ICR, a combination of SORI and on-resonance excitation (RE), termed SORI-RE. In comparison to SORI, this method produces more abundant ions resulting from higher energy fragmentation pathways. The result is the observation of a significant abundance of both higher and lower energy fragmentation pathways in the same mass spectrum. The comparison of SORI, RE, and SORI-RE spectra may lead to mechanistic insights as the relative abundances of certain fragment ions change as a function of internal energy deposition. This technique is simple to incorporate in existing instruments, does not require hardware or software modification, and requires only an additional 20-40 ms acquisition time. The technique is illustrated for a peptide (YGGFL), two disaccharides differing in the position of the glycosidic linkage (2alpha-mannobiose, 3alpha-mannobiose), an oligosaccharide (Alditol XT), a small protein (ubiquitin), and an inorganic cation (UO2+). Examples of higher energy fragmentation pathways enhanced by SORI-RE include the formation of immonium ions and oligosaccharide cross-ring cleavages.