Increasing numbers of proteins that have the capacity of interacting with protein kinase C isozymes in vitro and inhibiting their enzymatic activity in a noncompetitive manner have been purified. While these proteins can be hypothesized to be part of a tight regulatory system for protein kinase C enzymatic activity, critical examinations of the roles of these proteins in the context of whole cells have not yet been performed. Interesting new data suggest that some of the classes of protein kinase C inhibitors may have a much broader role of interacting with multiple types of kinases and proto-oncogene products. cDNAs encoding a number of these inhibitor proteins have been isolated, which will allow the design and implementation of experiments on their cell biology and help address their function outside of the context of their operational definitions.