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HyM is a hybrid methodology for the development of large-scale and complex integrated hybrid intelligent information systems, which combines traditional information system development methods with knowledge-based system development methods. The methodology is an integration of four existing methods using two integration process approaches: intra-process and inter-process. An intra-process approach is then used to integrate these techniques together using consistency rules. In the design phase, the inter-process approach is used to transform the requirements analysis to object-oriented design. Finally, the object-oriented method is applied to the design and implementation of hybrid information systems. This methodology takes advantage of the four individual methods to overcome the limitations of each. It is applicable to the development of traditional information systems knowledge-based systems, and large and complex cooperative and intelligent information systems. This paper describes the HyM methodology and its successful application when used to develop a hybrid intelligent information system in a complex medical domain.