A lattice-type Monte Carlo–based mesoscale model and simulation of the lithography process have been adapted to study the insoluble particle generation that arises from statistically improbable events. These events occur when there is a connected pathway of soluble material that envelops a volume of insoluble material due to fluctuations in the deprotection profile. The simulation shows that development erodes the insoluble material into the developer stream and produces a cavity on the line edge that can be far larger than a single polymer molecule. The insoluble particles can coalesce to form aggregates that deposit on the wafer surface. The effect of the resist formulation, exposure, postexposure bake, and development variables on particle generation was analyzed in both low- and high-frequency domains. It is suggested that different mechanisms are dominant for the formation of line-edge roughness (LER) at different frequencies. The simulations were used to assess the commonly proposed measures to reduce LER such as the use of low molecular weight polymers, addition of quenchers, varying acid diffusion length, etc. The simulation can be used to help set process variables to minimize the extent of particle generation and LER.