AC Milan's winning start to the Europa League was ended by a home defeat as Real Betis beat them at the San Siro.
The Italian club started top of Group F after back-to-back wins but were behind when Paraguay forward Antonio Sanabria tapped home inside the six-yard area.
Giovani Lo Celso doubled the Spanish side's lead in spectacular style, beating former Liverpool keeper Pepe Reina from 30 yards via the post.
Patrick Cutrone made it 2-1 but Milan then had Samu Castillejo sent off.
Betis lead by one point with three of their six group games played. Milan are second, two points ahead of third-placed Olympiakos, who picked up their first win by beating Luxembourg side Dudelange 2-0.
Elsewhere, Lazio extended their advantage over third-placed Marseille in Group H to five points by beating them 3-1 in France.
But Eintracht Frankfurt moved three points clear at the top of that group with a 2-0 victory over Apollon Limassol.
Five-time tournament winners Sevilla picked up their second win and moved top of Group J on goal difference after they thrashed Akhisarspor 6-0 and former leaders FK Krasnodar lost 2-1 at Standard Liege.
FC Zurich came from behind to beat Bayer Leverkusen 3-2 and maintain their 100% record in Group A after Karim Bellarabi had scored twice for the visitors.
In Group B, Red Bull Salzburg made it three wins from three with a 3-0 victory over Rosenborg and in Group C, Zenit St Petersburg fought back from a goal down to beat Bordeaux 2-1 at home, despite Artyem Dzyuba missing a penalty.
Fenerbahce overcame a 2-0 deficit to draw at Anderlecht in Group D, while Villarreal moved level on points with Rangers in Group G with an emphatic 5-0 win over Rapid Vienna.
KRC Genk moved top of Group I with a thrilling 4-2 win over Besiktas in Turkey, where five goals were scored in 17 minutes at the end of the second half.