Novak Djokovic launched his bid for a sixth title at the Miami Masters as crowd-pleaser Roger Federer was forced to withdraw prior to his first match in nearly two months with a stomach virus.
The Swiss, who underwent left knee surgery, was to have faced Juan Del Potro, who lost to Horacio Zeballos 6-4, 6-4.
Top seed Djokovic, winner of the last two editions, made short work of Briton Kyle Edmund 6-3, 6-3, winning his 25th of his last 26 matches in Miami with his only loss coming to Tommy Haas in 2013.
Djokovic improved to 23-1 on the season as he comes off his 27th record-levelling Masters 1000 crown from Indian Wells last weekend.
Federer, who will now likely make his return to tennis on clay in Monte Carlo in a fortnight, owns two Miami titles, the last one in 2006.
"I am very sorry that I have to pull out of the Miami Open with a stomach virus," Federer said. "I feel bad for the tournament and the fans as I have rarely ever had to withdraw at such short notice.
"I've not felt great for a few days and unfortunately it got worse in the last 24 hours. I was really excited to have my comeback in Miami but I am in no condition to play. I tried to warm up this morning but it was clear that I could not compete."
Spain's sixth seed David Ferrer came back a winner after resting at home for a month, schooling US teenager Taylor Fritz 7-6 (8-6), 6-1
The 11th seed Marin Cilic advanced to the third round over Serb Dusan Lajovic 6-4, 6-1 while Austrian Dominic Thiem, seeded 14th, beat Australian Sam Groth 7-5, 6-2. Belgian number 15 David Goffin beat Marcel Granollers 6-4, 6-4. Rafael Nadal said he is hoping to remedy a hole in his record after playing four Miami finals but failing to come up with a title.
"I've played well in my career here, no? Four finals, another semi-final, some more quarter-finals probably. So was a positive tournament for me. Only negative thing is I finally never win it," said the Spanish fifth seed.
Nadal said that compared to a year ago with his form and confidence scraping bottom, his feeling at the moment is one of optimism.
"The difference is I'm enjoying on court, I'm not feeling nerves on court. I'm not feeling that strange feeling that I never felt.
"I'm enjoying on the practises ... I feel with the right energy. I can lose, I can win, but I am happy on court.
In the women's draw, second seed Angelique Kerber won her first WTA match since beating Serena Williams for the Australian Open title two months ago, advancing past Czech Barbora Strycova 6-1, 6-1.
Wimbledon finalist Garbine Muguruza, seeded fourth, beat Dominika Cibulkova in a 6-7 (3-7), 6-3, 7-5 struggle while 2015 finalist Carla Suarez Navarro will lose a boatload of ranking points after losing her opening match to Coco Vandeweghe 6-4, 6-2.
Czech Kristina Pliskova advanced when Swiss seventh seed Belinda Bencic retired trailing 1-4 with back pain. Ninth-seeded US Open finalist Roberta Vinic defeated French Open runner-up Lucie Hradecka 1-6, 6-4, 7-6 (7-5)
Russian qualifier Elena Vesnina accounted for tenth seed and three-time winner Venus Williams 6-0, 6-7 (5-7), 6-2 with Williams losing serve nine times.
"I always enjoy my time on the court. I have a blast every single tournament, whether I win or lose," insisted the 35-year-old Williams.