In this study, the complications and ramifications of surface saturation and gas diffusion in measuring heterogeneous uptake coefficients of gases on powdered samples with a Knudsen cell reactor are discussed. Computer simulations show that for uptake on a single layer, when coverage and surface saturation effects are included. the measured initial uptake coefficient will depend on the escape constant, k(esc), of the Knudsen cell reactor and is a lower limit of the true initial uptake coefficient. For powdered samples with many layers, it is shown that gases can readily diffuse into the bulk of the powder. In many cases, surface saturation and diffusion occur on the same time scale and contribute to the total overall observed uptake. A layer-by-layer model has been developed for gas uptake on powdered samples. The model takes into account gas diffusion into the underlying layers and surface saturation of each layer. The model is used to explain experimental results for heterogeneous uptake of trace atmospheric gases on oxide and carbonate powders that are often used as laboratory surrogates for mineral dust.