An expanded paradigm for the diffuse rheumatic diseases is presented which focuses upon the integrated interactions of hormonal, immunological and vascular systems, i.e. the "H-I-V" triad. The reciprocal interactions between the (neuro)hormonal and immunological systems are increasingly recognized in experimental models and human examples of these diseases. Other important two-way interactions, e.g. between the hormonal and vascular systems, are also believed to be operating, but are relatively unexplored at present. An overview of the triad interactions between these vital regulatory systems of the body is offered. These interactions are further influenced by their relationships to broader genetic controls, physiological modulators, and environmental influences. Earlier, physiopathogenic stages of these evolving rheumatic disorders need to be understood, if prevention and optimal healing are to be achieved in the future.