The Dow Jones Industrial Average rose 19.80 points, or 0.06 percent, to 34,133.03. The S&P 500 lost 28.00 points, or 0.67 percent, to 4,164.66. The Nasdaq Composite Index fell 261.61 points, or 1.88 percent, to 13,633.50.
Six of the 11 primary S&P 500 sectors ended in red, with technology down 1.89 percent, leading the laggards. Materials climbed 1.04 percent, the best-performing group.
Shares of major U.S. tech giants, or the so-called FAANG group of Facebook, Apple, Amazon, Netflix and Google-parent Alphabet, all slipped.
U.S.-listed Chinese companies traded mostly lower with eight of the top 10 stocks by weight in the S&P U.S. Listed China 50 index ending the day on a downbeat note.
The above market reactions came as U.S. Treasury Secretary Janet Yellen said in an interview with The Atlantic aired on Tuesday that interest rates may have to increase to prevent the U.S. economy from overheating.
Yellen's comments came after the Federal Reserve last week kept its benchmark interest rates unchanged at the record-low level of near zero.
Jerome Powell, in his Fed Chair Press Conference last Wednesday, said that the economic recovery was happening faster than expected, but acknowledged the unevenness. He said that "it is not time yet" to talk about tapering the Fed's asset purchase program, as it will "take some time before we see substantial further progress" toward the central bank's employment and inflation goals.
On Monday, U.S. equities closed mixed, which saw the Dow and the S&P 500 score solid gains, while the Nasdaq declined, after data showed that the April U.S. manufacturing index missed expectations.
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