Direct staining with fluorescein-labelled human anti-Candida serum (ACFL) of extracellular Candida in trypsin-digested human tissues and in peritoneal exudates of mice showed brilliant green fluorescence of the cell wall of intact spores and mycelia. Candida organisms within human reticuloendothelial (RE) and tissue macrophages and within peritoneal polymorphonuclear cells of mice lacked a distinct cell wall by PAS stain and displayed a homogeneous, yellow-green fluorescence when stained with ACFL. These differences between the intact extracellular and the phagocytized organisms suggest that the outermost layer of the cell wall is removed by the phagocyte. The yellow-green fluorescence and homogeneous PAS-staining reaction observed are attributed to the middle layer of the cell wall which has been exposed by phagocytosis. Such a layer has been demonstrated in electron microscopic studies of yeast cell walls reported by various authors. The term “first stage spheroplast” is proposed for the intracellular organisms to indicate their intermediate position between the intact spore and the true spheroplast. The latter, obtained in vitro by digestion of Candida with glucuronidase-sulfatase, lacks both PAS and fluorescent antibody (FA) reactivity. It is postulated that further intracellular degradation of the “first stage spheroplast” results in rupture of the cell membrane and release of cytoplasmic particles into the tissues. These particles may furnish the cytoplasmic antigens that stimulate formation of precipitating antibodies which are characteristically demonstrable in systemic candidiasis. Rapid clearance of live Candida from the circulation and RE system of experimental animals suggests that demonstrability of Candida in human RE and tissue macrophages signifies recent entry of the organism into these sites. This may be the consequence of direct influx from the primary portal of entry, or of continuous hematogenous dissemination from candidal lesions in other internal organs. On the basis of these postulates, four major seropathologic patterns of systemic candidiasis are outlined, all of which have been observed ante- and postmortem in patients who had this infection.