Sales of new cars plunged 21.2% to 330,295 last month amid the worsening credit crunch and fears for the global economy, says the Society of Motor Manufacturers and Traders (SMMT).
It was the fifth consecutive fall, and came despite the introduction of new number plates, traditionally a time when owners think about trading up.
September registrations usually account for at least 17% of the annual total, so the figures are grim news for the industry.
Chief executive Paul Everitt said: "The fall in new-car registrations represents the most difficult economic conditions the industry has faced in 17 years.
"The Chancellor's pre-budget report should set out a package of measures to boost demand for new fuel efficient cars and scrap plans for unfair increases in vehicle excise duty."
Shadow transport secretary Theresa Villiers said: "These figures show that the nation's economic problems are by no means confined to the banking sector, but are spilling over into manufacturing as well.
"The Government needs to wake up to the serious problems in one of the most important parts of the UK's manufacturing industry and ensure that the regulatory climate doesn't make the situation worse for our hard-pressed vehicle manufacturers."
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