A method for treating mononuclear cells for an extracorporeal photopheresis procedure, driven and adjusted by a microprocessor-based controller, comprising the steps of priming a fluid circuit with priming fluid, directing whole blood derived from a blood source into the fluid circuit, separating the whole blood into a red blood cell component, a mononuclear cell component, and a plasma component, returning a first portion of the red blood cell component and a first portion of the plasma component to the whole blood, adding a photoactivation agent to the mononuclear cell component to create an agent-added mononuclear cell component, irradiating the agent-added mononuclear cell component to create a photoactivated mononuclear cell component, and incubating for a period of time a first portion of the photoactivated mononuclear cell component to create an incubated photoactivated mononuclear cell component.