(CNN) - CNN senior political analyst David Gergen said Tea Party favorite Christine O'Donnell's Delaware upset could spell trouble for the Republican Party.
O'Donnell knocked off former governor and nine-time U.S. Rep. Mike Castle in the GOP Senate primary on Tuesday.
"It's the clearest rebellion we've had all season. The biggest anti-establishment vote that's occurring against Republican candidates," Gergen said.
"One clear result out of Delaware is the chances of Republicans now gaining the Senate have gone down significantly. Delaware was an automatic pickup for Republicans before Mike Castle went down," he said.
National Republicans have already indicated they're not likely to rally around O'Donnell amid concerns that she has no chance of winning the seat – once held by Vice President Biden for 26 years – in November.
"For moderate Republicans who are thinking about a future in the GOP, when Mike Castle goes down ... when he goes down to a Tea Party candidate you've got a real insurgency going on in the party and it's leaving a lot of moderate Republicans tonight shaking their heads, not quite sure what the future of the party is," he said.