Interleukin-1 beta must be processed from its precursor form of 31.5 kDa to its mature form of 17 kDa in order to elaborate its wide array of bioactivities. The recent identification of a monocyte-specific endoprotease, termed interleukin-1 beta-converting enzyme (ICE), capable of generating authentic, bioactive 17 kDa IL-1 beta suggests that this protease may serve a specific role in the processing and subsequent secretion of IL-1 beta. To test this hypothesis, we describe initial attempts to establish a monocytic cell-based system to test if mutant preIL-1 beta molecules which are poor substrates for ICE in vitro will be processed and secreted by monocytic cells.