Blake will lead the U.S. team in the quarterfinals after Wimbledon finalist Andy Roddick withdrew because of a hip injury. Roddick pulled out Monday, a day after losing an epic five-set final to Roger Federer at Wimbledon.
"If you win, it relieves a lot of pressure for the second singles," Blake said after Thursday's draw for the best-of-five series.
The 6-foot-10 Karlovic reached the Wimbledon quarterfinals, losing to Federer. Karlovic served up a record 51 aces in a match last week at Wimbledon, and 55 at the French Open.
"You have to take chances of your rare opportunities against him, maybe in tiebreaks, and try to keep your serve," Blake said.
Mardy Fish, who replaced Roddick, will play Croatia's No. 1 Marin Cilic in the second singles on Friday.
Fish had to make last-minute schedule changes to arrive at the Croatian seaside resort.
"I'm obviously excited to fill in for Andy," he said. "That's my obvious role in the past couple of years."
This will be Croatia's fifth appearance in the quarterfinals, but it's bidding to reach the semifinals for the first time since winning the competition in 2005. Croatia has won 10 of its last 11 home ties.
Cilic, ranked No. 15, said Croatia's chances in the series are 50-50. He considers Mike and Bob Bryan, the top-ranked doubles team, as a major American advantage.
"Their almost assured victories in the doubles in the Davis Cup have a huge influence," Cilic said. "They give a major boost to the single players to make them more relaxed."
In doubles play Saturday, the Bryan twins will meet Karlovic and Lovro Zovko. In the reverse singles on Sunday, Cilic will play Blake and Karlovic will face Fish.
The United States, the 32-time champion, has never beaten Croatia in Davis Cup competition. The two nations have met twice, in 2002 and in 2005.
The U.S., the 2007 Davis Cup champion, is bidding to reach the semifinals for the fourth year in a row. Last year, the Americans lost to eventual champion Spain in the semifinals.
The winner of the best-of-five series will face the Czech Republic or Argentina in the semifinal in September.
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