US stocks ended weaker on Wednesday after US Federal Reserve Chair Janet Yellen warned of high valuations, adding to anxiety about future interest rates and a global bond rout.

The S&P 500 ended at a low not seen since early April after Yellen said high equity valuations could pose dangers, although she also said she does not see any bubbles forming.

Atlanta Federal Reserve bank president Dennis Lockhart said he still expects it will be appropriate to raise interest rates some time in the middle of the year, and that market expectations of a September increase were in "reasonable alignment" with the central bank's likely path.

His and Yellen's comments came as investors try to pinpoint when the Fed will begin raising interest rates for the first time since 2006. An April payroll report later this week may affect when the Fed will make its move.

"Everyone is obsessed with the Fed," said Michael Church, president of Addison Capital Management in Philadelphia. "It shouldn't surprise anyone that we didn't break out to new highs this week, given that you had Yellen speaking today and payrolls coming out on Friday."

Most of Wall Street's top banks see the Federal Reserve holding off until at least September before raising interest rates, based on Reuters' most recent poll.

A worldwide drop in government bond prices also spread unease to Wall Street.

"Markets can handle slowly, gradually-rising interest rates as an economy continues to improve. The uncertainty is that these are pretty significant moves," said Chuck Carlson, chief executive officer at Horizon Investment Services in Hammond, Indiana. "That's why you're starting to see stocks sell off a little more aggressively."

Cutting losses of more than 1 per cent in afternoon trade, the Dow Jones industrial average fell 86.22 points or 0.48 per cent to 17,841.98, the S&P 500 lost 9.31 points or 0.45 per cent to 2,080.15 and the Nasdaq Composite dropped 19.68 points or 0.4 per cent to 4,919.64.

Yellen's comments stung investors already nervous about stock prices. The S&P 500 currently trades at 17 times forward earnings, higher than its 10-year median of 15, according to Thomson Reuters StarMine.

With Wednesday's loss, the Dow was up just 0.11 per cent in 2015, while the S&P was up 1.03 per cent and the Nasdaq 3.88 per cent higher.

Apple was the biggest drag on the S&P 500 on Wednesday, down 0.63 per cent.

MoneyGram ended up 21.41 per cent after Western Union said it was not in talks to buy the company. Western Union gained 4.29 per cent.

Declining issues outnumbered advancing ones on the NYSE by 2,087 to 1,003, for a 2.08-to-1 ratio; on the Nasdaq, 1,455 issues fell and 1,285 advanced, for a 1.13-to-1 ratio favouring decliners.

The S&P 500 posted 7 new 52-week highs and 6 new lows; the Nasdaq Composite recorded 29 new highs and 73 new lows.

About 6.7 billion shares changed hands on US exchanges, below the 7.1 billion daily average for the last five sessions, according to BATS Global Markets.

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