The effects of chronic fluoride excess in the mouse were studied by means of polarizing microscopy in combination with a special staining technique employing Sirius red F3B, a dye which renders collagen fibrils sharply visible. It was observed that changes occur in three renal areas: the interstitium, the intrinsic vasculature and Bowman's capsule. The collagen content of each area increases after about 100 days of the total fluoride exposure of 280 days had elapsed. Although Bowman's capsule was thickened, the glomerular tufts and the nephrons showed edematous swelling and degeneration. A concept is developed to illustrate how early inflammatory response to the chemical effects of fluoride excess leads to vascular injury, parenchymal ischemia and fibrosis.