The losses were broad-based, but shares of manufacturing titans Boeing and Caterpillar were hit hard, slipping more than 1 percent on worries about higher input costs and trade barriers outside the United States.
General Electric dipped 1.3 percent after Deutsche Bank analysts warned of the potential impact from Trump's planned tariffs on steel and aluminium.
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"It's more of the same jitters we had seen recently, with investors, in this case, fearing that a lack of confidence in the tariffs by Trump's own people," said Andre Bakhos, managing director at New Vines Capital LLC in Bernardsville, New Jersey.
"Investors are taking risk off the table to see how much more damage in the administration this will cause."
Cohn, the architect of the tax overhaul enacted in December, was seen as a stabilizing force within the Trump administration. His departure is seen strengthening the hands of those advocating a protectionist agenda.
Also, driving losses were a set of weak results and forecasts from Dollar Tree and Ross Stores.
Discount store operator Dollar Tree slumped 14 percent after reporting disappointing holiday quarter results, while off-price retailer Ross Stores fell 7.4 percent after its full-year profit forecast came in largely below expectations.
Netflix's 1.2 percent drop after a "hold" rating from Stifel dragged the S&P consumer discretionary index down 0.84 percent.
At 9:32 a.m. ET, the Dow Jones Industrial Average was down 233.36 points, or 0.94 percent, at 24,650.76. The S&P 500 fell 0.69 percent to 2,709.19 and the Nasdaq Composite declined 0.59 percent to 7,328.45.
The ADP's National Employment Report showed that private employers added 235,000 jobs in February, compared with Reuters estimate of 195,000.
A more comprehensive report that includes hiring in both public and private sectors is due on Friday.
Declining issues outnumbered advancers on the NYSE by 2,005 to 457. On the Nasdaq, 1,765 issues fell and 502 advanced.
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