The mass dependence of the velocity distributions of analyte molecules in matrix-assisted laser desorption is analyzed based on the results of molecular dynamics simulations. The spread of the velocities along the direction of the flow is found to be independent of the mass of the analyte molecules and to reflect the entrainment of the analyte molecules in the expanding matrix. The radial velocity distributions for both matrix molecules and analyte molecules of different masses, on the other hand, fit well to a MaxwellBoltzmann distribution with the same temperature, suggesting the association of the spread in the radial velocities with the thermal motion in the plume. A consistent analytical description of the complete velocity distribution for matrix molecules and analyte molecules of different masses is proposed based on the approximation of a range of stream velocities and a single temperature in the ejected plume. # 1998 John Wiley & Sons, Ltd. Received 27 April 1998; Accepted 29 May 1998 Since the invention of matrix-assisted laser desorption/ ionization (MALDI) by Hillenkamp et al.