The S&P 500, along with the Nasdaq, reversed gains from earlier in the session, while MSCI's 47-country All World share index <.MIWD00000PUS> eked out a record high.
The Dow Jones transportation average <.DJT>, often seen as a gauge of the U.S. economy's health, fell 3.1 percent and hit its lowest point in nearly two months, while the S&P technology index <.SPLRCT> was down 0.8 percent, making it the day's worst-performing major group. The Nasdaq biotech index <.NBI> was down 1.9 percent.
Tech has been the best-performing sector this year, leading the S&P 500's 10.6 percent run in 2017.
"The general sentiment of the market coming into the day was that transportation stocks are telling us something that we're not paying attention to," said Art Hogan, chief market strategist at Wunderlich Securities in New York.
"You've got a general feeling a lot of good news is priced into this market," Hogan said.
The Dow Jones Industrial Average <.DJI> rose 85.54 points, or 0.39 percent, to 21,796.55; the S&P 500 <.SPX> lost 2.41 points, or 0.10 percent, to 2,475.42; and the Nasdaq Composite <.IXIC> dropped 40.56 points, or 0.63 percent, to 6,382.19.
"Biotech and tech are getting hit because they've been the outperformers. When people get nervous, they take money out of the outperformers first," said Ken Polcari, director of the NYSE floor division at O'Neil Securities in New York.
The biggest one-day drop in AstraZeneca (>> AstraZeneca) shares, following a drug study failure, dominated trading in Europe, though a handful of results helped broader indexes nudge higher. The pan-European STOXX 600 <.STOXX> ended down 0.11 percent.
In the U.S. Treasury and foreign exchange markets, investors continued to evaluate the Federal Reserve's recent statement that it is closer to paring its balance sheet.
The U.S. central bank said on Wednesday it expected to start winding down its massive holdings of bonds "relatively soon," despite striking a cautious tone on low inflation.
Many analysts and traders expect the Fed to announce its balance sheet reduction plans when its policymakers meet in September.
U.S. Treasury bond prices were weighed down by government and corporate debt supply. The Treasury Department sold $28 billion in seven-year notes to fair demand, the final sale of $88 billion in coupon-bearing supply this week.
U.S. benchmark 10-year Treasury notes
The U.S. dollar rose against the euro after U.S. data showing that new orders for key U.S.-made capital goods unexpectedly fell in June.
In the oil market, a rally in U.S. gasoline futures spurred further gains this week that came after key OPEC members pledged to reduce exports and the U.S. government reported a sharp decline in crude inventories.
Brent crude futures
(Additional reporting by Marc Jones in London, Sinead Carew in New York, Wayne Cole in Sydney; Editing by Bernadette Baum, Nick Zieminski and Jonathan Oatis)
By Caroline Valetkevitch