With an increasing number of technologies supporting transactions over distance and replacing traditional forms of interaction, designing for trust in mediated interactions has become a key concern for researchers in human computer interaction (HCI). While much of this research focuses on increasing users’ trust, we present a framework that shifts the perspective towards factors that support trustworthy behavior. In a second step, we analyze how the presence of these factors can be signalled. We argue that it is essential to take a systemic perspective for enabling well-placed trust and trustworthy behavior in the long term. For our analysis we draw on relevant research from sociology, economics, and psychology, as well as HCI. We identify contextual properties (motivation based on temporal, social, and institutional embeddedness) and the actor’s intrinsic properties (ability, and motivation based on internalized norms and benevolence) that form the basis of trustworthy behavior. Our analysis provides a frame of reference for the design of studies on trust in technology-mediated interactions, as well as a guide for identifying trust requirements in design processes. We demonstrate the application of the framework in three scenarios: call centre interactions, B2C e-commerce, and voice-enabled on-line gaming.