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Initial growth of Nocardia corallina occurred by germination and coenocytic hyphal development which resulted in a large surface-to-volume increase. During this period, endogenous respiration and the ability to oxidize fructose increased rapidly, but the stimulation of oxygen uptake by glucose decreased to zero. This inability to utilize glucose was due to loss of permeability rather than lack of a specific enzyme required for glucose metabolism. This was established by the following data: (1) cell-free extracts of hyphae contained the enzymes for conversion of glucose into fructose-6-phosphate; (2) intact hyphae oxidized fructose; (3) incubation of hyphae with cetyltri-methylammonium bromide increased cell permeability to glucose and oxygen uptake was stimulated. Comparative determinations of enzymes involved in the early steps of glucose metabolism showed quantitative changes associated with the period of impermeability to glucose. The loss of permeability to glucose may represent an initial metabolic change fundamental to morphogenesis in this microbe.