Pro-inflammatory caspase-1 is a key player in innate immunity. Following activation in heterogenic protein complexes called the inflammasome , caspase-1 processes IL-1β and IL-18 to their mature forms and triggers pyroptosis. Here, we describe a small-volume whole blood assay facilitating the measurement of caspase-1 activity and inflammasome-related gene expression following specific stimulation of either the NLRP3, NLRC4, or AIM2 inflammasome .