We employed the grounded theory method to construct a framework describing the distinctive mechanisms through which big-science centers generate industrial knowledge spillovers in the economy. Our focus is on large-scale big-science installations typically associated with experimental physics. We draw on social network, social capital, and inter-organizational learning theories to examine knowledge spillovers accruing to industrial partner companies in big-science-industry dyads. The context for the study is provided by CERN's new particle accelerator project, the Large Hadron Collider (LHC). In addition to building a grounded theory framework for the study of industrial knowledge spillovers, our study demonstrates the distinctive potential that big-science centers offer as a source of knowledge spillovers in national innovation systems.