A strain of Escherichia coli O6:H-, which was isolated from a patient with acute pyelonephritis, was used to produce ascending pyelonephritis in mice. The histologic features at the early stage of acute pyelonephritis and the pathways of bacterial invasion and distribution in the infected kidneys were studied by using transmission electron microscope. The histologic changes were characterized by degeneration and destruction of renal pelvic and tubular epithelial cells, and a massive infiltration of polymorphonuclear leukocytes. Bacteria invaded the pelvic surface and spread over the renal medulla and cortex by contiguity twelve hours after infection. It was also shown that bacteria ascended the tubules, multiplied in the tubular lumina, destroyed the tubular epithelial cells, and spread over the renal cortex by twelve hours. In addition, bacteria and leukocytes phagocytizing bacteria were present in the capillaries in the renal interstitium twelve hours after infection.