The doubles winning streak of Nick Kyrgios and Thanasi Kokkinakis has been halted, with the Australian Open champions losing in the round of 16 in Indian Wells.

Kyrgios and Kokkinakis entered the match against fellow wildcards John Isner and Jack Sock on the back of seven straight wins as a pairing.

But the experienced American duo — both former top-10 singles players — came out on top with a 6-3, 7-6 (7-3) triumph.

The Australians were playing together in doubles in California for the first time since their remarkable victory at Melbourne Park in January.

Kyrgios is still in the men's singles draw and he will face world number eight Casper Ruud in the round of 32 on Tuesday AEDT.

Among other Australian results in Indian Wells, Alex de Minaur defeated John Millman 7-6 (7-4), 6-3.

Millman made the Australian men's number one fight to take the initiative in a first-set tiebreaker.

But continuing in the form that helped him star in Australia's Davis Cup qualifying victory over Hungary this month, 29th seed de Minaur eventually prevailed in an hour and 40 minutes.

De Minaur next plays unseeded American Tommy Paul for a place in the last 16.

Paul enjoyed an upset victory over Alexander Zverev with a 6-2, 4-6, 7-6 (7-2) defeat of the world number three.

Zverev was making his first appearance at an ATP tournament since being placed on a suspended ban for his infamous outburst at the Mexican Open, which the German described as "the biggest mistake" of his tennis career.

Another Australian, Jordan Thompson, lost in straight sets to Grigor Dimitrov, with the 33rd-seeded Bulgarian winning 7-6 (7-3), 6-2.

Earlier on Monday AEDT, 31st-seeded Kazakhstani Alexander Bublik got revenge against Andy Murray by beating the Scot 7-6 (11-9), 6-3 to notch his first win over the former world number one in three career meetings.

Andrey Rublev — seeded seventh in Indian Wells — accounted for Dominik Koepfer 7-5, 6-4 for his 10th straight victory.

ABC/Wires