An isolated sciatic nerve preparation was used to measure the transport rates of more than 18,000 vesicles in 72 axons from young (3-4 months of age) and old (24-26 months of age) rats from two strains (Harlan Sprague-Dawley and Fisher-344). Average anterograde and retrograde vesicle transport rates were significantly slower in the older animals. The amount of slowing of anterograde vesicles was twice as great as the slowing of retrograde vesicles. Age-related slowing of vesicle transport was inversely proportional to vesicle speed, with the result that transport of the slowest and largest vesicles may essentially be blocked in older axons. One possible explanation for these data is that long-lived axonal cytoskeletal proteins are subject to age-related changes that impede vesicle transport.