The dominant noises present in sequential, two-photon photoionization, in polar solvent systems under HPLC conditions, are discussed. Several representative chromatograms for the separation and detection of five benzodiazepines are exhibited, showing the effectiveness of a baseline restorer preamplifier relative to an ordinary, low-noise, AC-coupled preamplifier. It is found that there isnooptimum preamplifier, particularly where solvent programming applications are necessary. The observed dominant noises in polar solvents are related to the leakage currents that result when high voltages are impressed across the polar solvent systems, but the precise nature of the relationship is unknown.