Neurons in vivo receive a large amount of internally generated “background” activity in addition to synaptic input directly driven by an external stimulus. Stimulus-driven and background synaptic inputs interact, through the nonlinearities of neuronal integration, in interesting ways. The dynamic clamp can be used in vitro to duplicate background input, allowing the experimenter to take advantage of the accessibility of neurons in vitro while still studying them under in vivo conditions. In this chapter we discuss some results from experiments in which a neuron is driven by current injection that simulates a stimulus-driven input as well as dynamic-clamp-generated background activity. One of the effects uncovered in this way is multiplicative gain modulation, achieved by varying the level of background synaptic input. We discuss how the dynamic clamp was used to discover this effect and also how to choose parameters to simulate in vivo background synaptic input in slice neurons.