The cars were first introduced in 1969 as part of the B/M/T Broadway line, which became the N line.
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They were also the first cars with air conditioning.
Most of the R-42s were retired between 2006 and 2009.
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On Wednesday, the remaining few made their final runs on the A line before being officially retired.
The cars have been used on two dozen lines, each traveling more than seven million miles. They had a memorable role in an iconic car-vs.-train chase in the classic 1971 film "French Connection."
The final run was followed a sendoff ceremony at the New York Transit Museum.
"These cars have served the MTA well as a reliable fleet over the last 50 years," said Sally Librera, senior vice president, department of subways. "As technology advances, we're looking to modernize our fleet of subway cars to best serve New Yorkers."
The R-42s were built by the St. Louis Car Company and were the first cars received by the newly branded MTA in 1969, eventually totaling 400 cars in the NYC Transit fleet.
The R-42 was the last car type to be designed as "married pairs," which means every two cars are semi-permanently linked together in order to reduce the amount of components that are required to operate a train.
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