The mechanism for photoionization of the phenothiazine derivatives, promazine and chlorpromazine, has been studied as a function of solvent and excitation conditions. Sequential biphotonic absorption is responsible for photoionization induced by pulsed laser irradiation at 308 or 355 nm. In order to determine the excited states involved excitation was carried out under conditions where the second photon was exclusively absorbed by the lowest excited singlet state (using picosecond excitation pulses where the pulse duration is much less than singlet lifetime) or by the lowest triplet state using a two-color, two-pulse excitation protocol. Photoionization occurs upon two-photon excitation within the singlet manifold in aqueous solutions and methanol. In addition, photoionization is solvent dependent upon excitation of the triplet state at 355 nm or near its absorption maximum of 460 nm. In water the triplet absorption was bleached concomitant with the generation of absorption from the radical cation and hydrated electron. Quantum yields of photoionization of promazine were 0.02 and 0.03 in acetonitrile and water, respectively. In methanol or other alcohols, photoionization was not observed under the same excitation conditions. Triplet lifetimes, molar absorption coefficients, and quantum yields of intersystem crossing were determined in various solvents. The experimental results indicate that during single wavelength pulsed irradiation of these compounds, the second photon is absorbed predominantly by the lowest excited singlet state rather than the lowest excited triplet state. The energetics of the photoionization of promazine and chlorpromazine were estimated as a function of solvent.