Methods of enhancing the spectral selectivity for identification and quantitation of molecules in complex systems, such as polynuclear aromatic hydrocarbons (PAHs) in environmental samples or drugs in biological materials, are mentioned. The major emphasis concerns the description of the instrumentation and analytical figures of merit for a three-mode cuvette and a three-mode flow cell detection system based upon fluorescence, photoacoustic, and photoionization detection. The instrumental system consisting of a laser (nitrogen [N₂] laser or N₂-dye laser), the cell assembly, and the detection system is briefly described for all three modes for each type of cell. Limits of detection for the three modes are given and compared for several selected molecules. A model five-compound mixture is separated by high-performance liquid chromatography (HPLC) and detected with the three-mode flow detector. The mechanism of the photoionization detection is briefly discussed.