Microorganisms interact chemically in natural environments; however, the compounds and mechanisms involved in this phenomenon are still poorly understood. Using the cocultivation approach, changes in metabolic profiles due to interactions between endophytic fungal and actinobacterial strains isolated from the plant Lychnophora ericoides (Asteraceae) were assessed. The production of the cytotoxic compound cytochalasin H by the fungus Phomopsis sp. FLe6 was remarkably inhibited in solid and liquid co-cultures with the actinobacteria Streptomyces albospinus RLe7. This was a consequence of the fungal growth inhibition caused by antifungal compounds produced by S. albospinus RLe7, including amphotericin B. Cytochalasin H is not toxic to S. albospinus RLe7, suggesting that this microorganism does not require a defense mechanism to prevent the potentially harmful effects of such fungal compound. By exhibiting various competitive phenotypes, these microbes can control each other's growth when sharing an environment.