Injection of killed tubercle bacilli into a sensitised guinea pig produces a characteristic biphasic response with the development of an organised epithelioid cell granuloma in the second phase. Previous sensitisation to tubercle bacilli is a requirement for development of the organised granulomatous response. The main components of the granuloma are epithelioid cells, although multinucleate cells of both Langhans and foreign-body type are present. Epithelioid cells appear to evolve from monocytes, probably in the sequence: (a) monocyte, (b) monocytic transition form, (c) immature epithelioid cell, (d) mature epithelioid cell, although some may possibly develop through a macrophage stage. Differentiation of monocytes into epithelioid cells is a continual process in the experimental tuberculous granuloma with monocytes migrating into the lesion at all stages examined. Epithelioid cells are not obviously phagocytic. Their differ4ntiation has a phase suggestive of biosynthesis during which RER is the predominant cytoplasmic component. This is followed by a storage/secretory phase in which the cytoplasm contains membrane-lined vesicles and prominent Golgi apparatus. The vesicles and, where distended, the RER laminae contain a lightly staining, finely granular material the biological activity of which is unknown.