In women with clue-cell-positive discharge (CCPD), light-microscopical examination of the wet mount suggests a preference of bacteria for certain vaginal epithelial cells (VECs). To investigate this further, a light- and electron-microscopical study of patients and healthy controls was performed, with special emphasis on vitality and glycogen content of VECs and bacterial-epithelial cell interaction. Our study did not reveal morphologic differences between VECs of patients and controls. There was, however, a significant decrease in the percentages of vital and glycogen-containing VECs in CCPD (p < 0.001), probably caused by an overgrowth of (anaerobic) bacteria. In CCPD vaginal bacteria preferably colonize vital VECs. This could account for the relatively low percentage of clue cells in this condition.