Italy may be World Cup winners but AC Milan and Chievo have plenty of work to do if they are to reach this year's Champions League proper.
Milan, allowed into the Champions League despite their involvement in a domestic match-fixing scandal, take a 1-0 lead to Serbia for the second leg of their match with Red Star Belgrade in a fortnight.
Filippo Inzaghi scored the only goal in the first leg at the San Siro.
Chievo must overturn a 2-0 deficit when they host Levski Sofia in their second leg match in Verona.
A late penalty from Frenchman Cedric Bardon completed the win for the Bulgarians who had taken the lead through Valeri Domovchiyski.
French Lille took a giant stride towards the Champions League proper when they beat Rabotnicki Skopje 3-0 in the first leg, thanks to a Dalibor Jovanovski own goal, a penalty from Fernandes Michel Bastos, and Nicolas Fauvergue's strike.
Elano Blumer's 39th-minute penalty gave Ukrainian champions Shakhtar Donetsk a 1-0 lead after their first-leg match with Polish visitors Legia Warsaw.
Another Ukrainian side Dynamo Kiev were convincing 3-1 victors over Turkish outfit Fenerbahce.
Galatasaray fared better than their Istanbul neighbours by thrashing Mlada Boleslav 5-2, with two goals from Arda Turan, and veteran Hakan Sukur also on the scoresheet.
CSKA Moscow, winners of the 2005 UEFA Cup, took a 3-0 lead by winning their first leg match at home to Slovakia's SCP Ruzomberok.
Czech champions Liberec and Russia's Spartak Moscow drew their first-leg match 0-0.
Former European champions Steaua Bucharest came back to draw 2-2 with Belgian hosts Standard Liege.
Spanish outfit Osasuna are competing in the Champions League for the first time and will fancy their chances after coming away from Hamburg with a 0-0 first-leg draw.
Ajax had prolific marksman Klaas-Jan Huntelaar to thank for their 2-1 away win at FC Copenhagen.
Huntelaar, who scored 33 Eredivisie goals for Heerenveen and Ajax last season but was overlooked for the World Cup by Holland coach Marco van Basten, opened the scoring after 37 minutes.
The Danes equalised through Brede Hangeland on the stroke of the break but Huntelaar's second sealed the first-leg win for the four-time European champions.
Austrians Salzburg pulled off a stunning 1-0 first leg win over Valencia.
Salzburg, benefiting from a cash injection from sponsors Red Bull, appointed former Italy coach Giovanni Trapattoni in the summer.
And the old maestro will be looking forward to the second leg in Spain after Karel Pitak secured the win for the Austrians with a 73rd-minute striker.