ABSTRACT. Quantitative and qualitative relationships were found between secreted proteins and their activity, and the hyphal morphology of Moniliophthora perniciosa, the causal agent of witches' broom disease in Theobroma cacao. This fungus was grown on fermentable and non-fermentable carbon sources; significant differences in mycelial morphology were observed and correlated with the carbon source. A biological assay performed with Nicotiana tabacum leaves revealed that the necrosis-related activity of extracellular fungal proteins also differed with carbon source. There were clear differences in the type and quantity of the secreted proteins. In addition, the expression of the cacao molecular chaperone BiP increased after treatment with secreted proteins, suggesting a physiological response to the fungus secretome. We suggest that the carbon source-dependent energy metabolism of M. perniciosa results in physiological alterations in protein expression and secretion; these may affect not only M. perniciosa growth, but also its ability to express pathogenicity proteins.