Particulate flows have mainly been studied under the simplifying assumption of a one-way coupling regime where the disperse phase does not modify the carrier fluid. A more complete view of multiphase flows can be gained calling into play two-way coupling effects, i.e. by accounting for the inter-phase momentum exchange, which is certainly relevant at increasing mass loading. In this paper we present a new methodology rigorously designed to capture the inter-phase momentum exchange for particles smaller than the smallest hydrodynamical scale, e.g. the Kolmogorov scale in a turbulent flow. The momentum coupling mechanism exploits the unsteady Stokes flow around a small rigid sphere, where the transient disturbance produced by each particle is evaluated in a closed form. The particles are described as lumped point masses, which would lead to the appearance of singularities. A rigorous regularization procedure is conceived to extract the physically relevant interactions between the particles and the fluid which avoids any ‘ad hoc’ assumption. The approach is suited for high-efficiency implementation on massively parallel machines since the transient disturbance produced by the particles is strongly localized in space. We will show that hundreds of thousands of particles can be handled at an affordable computational cost, as demonstrated by a preliminary application to a particle-laden turbulent shear flow.