Certain biological reactions, such as receptor-ligand binding at cellcell interfaces and macromolecules binding to biopolymers, require many smaller molecules crowding a reaction site to be cleared. Examples include the T cell interface, a key player in immunological information processing. Diffusion sets a limit for such cavitation to occur spontaneously, thereby defining a timescale below which active mechanisms must take over. We consider N independent diffusing particles in a closed domain, containing a sub-region with N0 particles, on average. We investigate the time until the sub-region is empty, allowing a subsequent reaction to proceed. The first passage time is computed using an efficient exact simulation algorithm and an asymptotic approximation in the limit that cavitation is rare. In this limit, we find that the mean first passage time is subexponential, T ∝ e N 0 /N 2 0 . For the case of T cell receptors, we find that stochastic cavitation is exceedingly slow, 10 9 seconds at physiological densities, however can be accelerated to occur within 5 second with only a four-fold dilution.Diffusion drives many biological processes, both positively, by delivering cargo to a target, and negatively, by removal of cargo from a region of interest (ROI). While the temporal dynamics of diffusional delivery have been extensively studied [5,4,24,12], diffusion-driven removal has been less characterized experimentally or theoretically [3]. Removal is of particular interest in the crowded environment of cells, where large biomolecules and cellular structures require the displacement of smaller molecules, a phenomenon we term stochastic cavitation.A specific example arises in the study of cell-cell interfaces including the T-cell/antigen-presenting-cell interface [22,2,29,8] (see Fig. 1). A fundamental question for all cell-cell interfaces is how receptors and ligands come into