The Corvette was replaced every three thousand miles. Chevrolet was the show's sponsor. It was never explained how Tod was able to get a new Corvette so often.
One memorable episode featured Boris Karloff, Lon Chaney, Jr., and Peter Lorre. Karloff and Chaney were given the chance to don their famous Universal Frankenstein Monster and Wolf Man make-up for the first time in a few decades.
Although the series was called "Route 66", many of the episodes were set in areas in the United States, through which Route 66 did not travel. For example, Route 66 begins in Chicago and ends in Los Angeles, or vice versa, but two episodes were shot in New England, one in Maine, season four,, episode two, "Same Picture, Different Frame", and one in Vermont, season four, episode three, "Come Out, Come Out, Wherever You Are". Both aired in the fall of 1963, and starred Martin Milner and Glenn Corbett.
The Corvette was never red, as often believed. It was light blue in the first season, beige in the second season, and tan in the third season. The colors were chosen because they photographed well in black and white.
Three future movie stars nearly became regulars on this series. When the show was first getting off the ground, a young unknown named Robert Redford auditioned for the role of Tod Stiles, but was beaten out by Martin Milner. When George Maharis left the show in late 1962, the producers searched for a replacement. Burt Reynolds was approached, but he was then involved on Gunsmoke (1955) playing Quint Asper. Another actor who wanted to do the series, was future Academy Award winner Robert Duvall, who was even auditioned in one episode. The producers felt that Duvall was not handsome enough, however, and went with Glenn Corbett instead.