For decades, granulomas have been considered as enigmatic tissue reactions. The granulomatous manifestations of various diseases have been interpreted as non-specific reactions to tissue irritants. The term ‘granuloma’itself was coined by Virchow who described the granuloma as:‘a tumorlike mass, or nodule, of granulation tissue’[102]. Dermatologists define the granulomatous inflammation as a focal, chronic inflammatory response to tissue injury evoked by a poorly soluble substance [117]. The definition, recently suggested by Warren [426], which describes the granuloma as a ‘focal chronic inflammatory reaction characterized by the accumulation and proliferation of leukocytes principally of the mononuclear type’is preferred.

In this review, I intend to discuss and correlate the various observations that had been contributed by several laboratories. Special emphasis will be given to the experimental hypersensitivity granulomas. These advances greatly furthered our understanding of the etiology, cellular mechanisms, and function of the granulomatous inflammations. The cellular complexity of the granuloma, its dynamic state, the intricacies of cell-cell interactions, the generation of inhibitory and facilitating signals, as well as the manifold role of the lesion in the health/disease state of the individual, however, still pose a profound challenge to the researchers of the field. A list of some of the granulomatous diseases is given in table I. As one can see, the etiologic agents range from live, replicating intracellular organisms (bacteria, fungi, viruses) through non-replicating metazoans (worms) to inanimate metals. Furthermore, in a large group of diverse