Mainstream computing equipment and the advent of affordable multi-Gigabit communication technology permit us to address grand-challenge data acquisition and processing problems with clusters of inexpensive computers. Such networks typically incorporate heterogeneous equipment, real-time partitions and even custom devices. Vital overall system requirements are high efficiency and flexibility. In preceding projects we experienced the difficulties to cover both requirements at once. Intelligent I/O (I₂O) is an industry specification that defines a uniform messaging format and execution environment for hardware- and operating system independent device drivers in computing systems with processor based communication equipment. Mapping this concept to a distributed computing environment and encapsulating the details of the specification into an application-programming framework allow us to provide architectural support for (i) efficient and (ii) extensible cluster operation. This paper portrays our view of applying I₂O to high-performance clusters. We demonstrate the feasibility of this approach by giving efficiency measurements of our XDAQ software framework for distributed data acquisition systems.