Ireland's Dan Martin will miss the rest of the Giro d'Italia after breaking his collarbone in a crash in the opening team time trial stage in Belfast.
The 27-year-old Garmin-Sharp rider went down after riding over a manhole cover in wet conditions, taking out several team-mates in the process.
Rigoberto Uran and Cadel Evans fared best of the pre-race favourites, with their teams second and third.
Australia's Orica GreenEdge won, with Svein Tuft taking the race lead.
Canadian Tuft led the squad over the line on his 37th birthday, and will therefore wear the race leader's pink jersey on stage two.
The five team-mates who finished with him are credited with the same time.
"It's an amazing day," Tuft told BBC Sport. "This is a pretty crazy way to spend your birthday and I can't thank the team enough for giving me the opportunity. It's the chance of a lifetime for a rider like me.
"This is a special day. The team gave me a great birthday present."
This is just the 11th time the Giro has started outside Italy, and the first time the race has started outside continental Europe, and it could scarcely have begun in more dramatic fashion.
Sporadic rain and a damp road made for tricky conditions on the 21.7km route around the Northern Irish capital and Martin, who has made the Giro his main focus of the season, went down on a seemingly innocuous straight section of road.
He lost control as he went over a manhole cover and was left sitting on the side of the road, clutching his right shoulder.
Garmin-Sharp manager Jonathan Vaughters tweeted: "So sad. Nothing to be done. Professional bike racing is cruel."
A statement from the team said Martin "continues to be evaluated for additional injuries".
Uran's Omega Pharma - Quick-Step team, one of the later starters, finished just five seconds down on Orica, while Evans's BMC Racing squad were two seconds further adrift in drying conditions.
Ireland's Nicolas Roche, who is hoping for a top three finish at the end of the three-week race, was fourth with his Tinkoff - Saxo team, while sole Briton Ben Swift is 35 seconds off the pace after Team Sky were fifth.
Colombia's Nairo Quintana, who is favourite to win his first Grand Tour title, finished 55 seconds behind Orica with his Movistar team, to leave him 50 seconds adrift of Uran and 48 behind Evans.
Joaquim Rodriguez was another of the day's big losers, finishing 93 seconds down on the leaders and more than a minute behind most of his rivals.
Saturday's second stage starts and ends in Belfast, after visiting the Giant's Causeway.
Stage one result:
1. Orica GreenEdge (Aus) 24:42"
2. Omega Pharma - Quick-Step (Bel) +5"
3. BMC Racing (US) +7"
4. Tinkoff - Saxo (Rus) +23"
5. Team Sky (GB) +35"
6. Astana (Kaz) +38"
7. Cannondale (Ita) +53"
8. Movistar (Spa) +55"
9. Giant-Shimano (Ned) +56"
10. AG2R (Fra) +58"
1. Svein Tuft (Can/Orica GreenEdge) 24:42"
2. Luke Durbridge (Aus/Orica GreenEdge) same time
3. Pieter Weening (Ned/Orica GreenEdge)
4. Cameron Meyer (Aus/Orica GreenEdge)
5. Michael Matthews (Aus/Orica GreenEdge)
6. Ivan Santaromita (Ita/Orica GreenEdge)
7. Pieter Serry (Bel/Omega Pharma - Quick-Step) +5"
8. Gianluca Brambilla (Ita/Omega Pharma - Quick-Step)
9. Rigoberto Uran (Col/Omega Pharma - Quick-Step)
10. Serge Pauwels (Bel/Omega Pharma - Quick-Step)