This paper reports on the structure and ultrastructure of the ventricular myocardium of the African lungfish Protopterus dolloi in freshwater (FW), in aestivation (AE), and after the AE period. The myocardium shows a conventional myofibrillar structure. All the myocytes contain large intracytoplasmic spaces occupied by a pale material that could contain glycosaminoglycans and/or glycogen, which may be used as food and water reservoirs. In FW, the myocytes in the trabeculae associated with the free ventricular wall show structural signs of low transcriptional and metabolic activity (heterochromatin, mitochondria of the dense type). These signs are partially reversed during the AE period (euchromatin, mitochondria with a light matrix), with a return to the FW appearance after arousal. The myocytes in the septum show, in FW conditions, nuclear polymorphism (heterochromatin, euchromatin), and two types (colliquative and coagulative) of necrosis. In AE, all the septal myocytes show euchromatin, and the number of necrotic cells increases greatly. Cell necrosis appears to be related to the septal architecture. After arousal, the septal myocytes exhibit a heterochromatin pattern, the number of necrotic cells decreases, cell debris accumulates under the endocardium, and phagocytosis takes place. Despite being a morphologic continuum, the trabeculae associated with the free ventricular wall appear to constitute a different compartment from that formed by the trabeculae in the ventricular septum. Paradoxically, AE appears to trigger an increase in transcriptional and synthetic myocardial activities, especially at the level of the ventricular septum. This activity may be involved in mechanisms of autocrine/paracrine regulation. Aestivation cannot be regarded as the result of a general depression of all cellular and organic activities. Rather, it is a much more complex state in which the interplay between upregulation and downregulation of diverse cell activities appears to play a fundamental role.