Thirty-six mucosal specimens were obtained with a biopsy instrument from the upper nasal septum of 12 human autopsy cases before the en bloc removal of the entire olfactory area. Examination of these 36 specimens with transmission electron microscopy demonstrated olfactory epithelium in only 17. A significant negative correlation (r = -.728) was noted between the age of the subject and the probability of obtaining olfactory epithelium, supporting the idea that the olfactory mucosa is gradually replaced by respiratory epithelium with aging. Using the en bloc specimens, the distribution of olfactory epithelium was reconstructed from light microscopic examination of silver-stained sections. Multiple patches of respiratory epithelium were observed over the upper portion of the nasal septum and superior turbinates, ie, the presumptive olfactory area. On transmission electron microscopic examination, frequent respiratory metaplasia was also suggested. Within the area of respiratory metaplasia, supporting cell-like and microvillar cell-like structures often were found; these structures may be remnants of olfactory epithelium. The sampling of olfactory tissue with a biopsy procedure is hampered by the irregular and patchy distribution of olfactory epithelium. The invasion of respiratory epithelial patches into the olfactory mucosa seems to be characteristic of the human olfactory epithelium and may increase as a function of age. Thus, conclusions about the structure of the olfactory mucosa in an individual patient must be based on several tissue samples.