Argentina's defence of the Davis Cup title looks set to end less than three months after they finally won the trophy for the first time.
Without talisman Juan Martin del Potro, who is starting his season late as a result of his exertions in beating Croatia in November, they could offer little resistance in front of their home fans in Buenos Aires and trail Italy 2-0.
Guido Pella lost 6-3 6-3 6-3 to Paolo Lorenzi before Andreas Seppi defeated Carlos Berlocq 6-1 6-2 1-6 7-6 (8/6).
The main talking point in the build-up to the first-round ties has once again been the absence of the sport's big names.
World number Novak Djokovic was the only member of the top 10 in action, and for a while against Russia's Daniil Medvedev he may have wished he had followed his rivals in sitting out the week.
Medvedev, at 20 an up-and-coming talent, led by a set and 3-0 but Djokovic recovered to win by retirement when leading 3-6 6-4 6-1 1-0 after his opponent was dramatically struck down by cramp.
After his shock loss to Denis Istomin at the Australian Open, Djokovic is no doubt hoping a week with team-mates in front of an adoring crowd in Nis can help him rediscover his best form.
It was a good day all round for Serbia, with Viktor Troicki having saved a match point to beat another young talent Karen Khachanov 6-4 6-7 (3/7) 6-3 1-6 7-6 (6/8) in the opening rubber.
Last year's runners-up Croatia are missing their four leading players but Franko Skugor, the highest-ranked team member at 223, rose to the challenge with a 3-6 6-3 6-4 4-6 7-6 (8/6) victory over 26th-ranked Pablo Carreno Busta of Spain.
The visitors levelled at 1-1 when Roberto Bautista Agut defeated Ante Pavic 6-4 6-2 6-3 and remain heavy favourites to progress.
Debutant Jordan Thompson upstaged Nick Kyrgios as Australia eased into a 2-0 lead over the Czech Republic at Melbourne's historic Kooyong Club.
After his 6-3 6-3 6-4 win over Jiri Vesely, Thompson said on daviscup.com: "(It was) U nbelievably satisfying. That was the best feeling in my life."
Kyrgios fulfilled his part of the bargain by beating Czech debutant Jan Satral 6-2 6-3 6-2.
There were no upsets in Tokyo, where Richard Gasquet and Gilles Simon both won in straight sets against Taro Daniel and Yoshihito Nishioka, respectively, to put France 2-0 up against Japan.
Germany and Belgium, meanwhile, are tied at 1-1.
Davis Cup specialist Steve Darcis shocked Philipp Kohlschreiber in dramatic fashion, winning 6-4 3-6 2-6 7-6 (7/2) 7-6 (5/7), but Alexander Zverev restored equilibrium with a 6-3 6-3 6-4 win against Arthur De Greef.