Rarely observed nanoparticle dissolution rate data have been collected and explained for an environmentally and industrially relevant nanomaterial (PbS, the mineral galena) as a function of its particle size and aggregation state using high-resolution transmission electron microscopy (HRTEM) and solution analysis. Under identical anoxic acidic conditions (pH 3 HCl), it has been determined that the dissolution rate of PbS galena varies by at least 1 order of magnitude simply as a function of particle size, and also due to the aggregation state of the particles (dissolution rates measured are 4.4 × 10−9 mol m−2 s−1 for dispersed 14 nm nanocrystals; 7.7 × 10−10 mol m−2 s−1 for dispersed 3.1 μm microcrystals; and 4.7 × 10−10 mol m−2 s−1 for aggregated 14 nm nanocrystals). The dissolution rate difference between galena microparticles and nanoparticles is due to differences in nanotopography and the crystallographic faces present. Aggregate vs. dispersed dissolution rates are related to transport inhibition in the observed highly confined spaces between densely packed, aggregated nanocrystals, where self-diffusion coefficients of water and ions decrease dramatically. This study shows that factors at the nanometer scale significantly influence the release rate of aqueous, highly toxic and bioavailable Pb in natural or industrial environments during galena dissolution.