A group of people were gathered for a party at a home on Oleander near 22nd just before 7:30 pm. A car pulled up to the house.
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"According to witnesses, the subject got out of a vehicle, walked up to the crowd, and began firing indiscriminately at different persons," Delano Police Chief Robert Nevarez said.
Police said an 11-year-old and a 12-year-old girl were killed. Their names have not been released.
Three other adults - a man and two women - were also shot, but suffered non-life-threatening injuries, officials said.
Investigators said the style of shooting is consistent with gang shootings they've seen in the recent past.
No arrests have been made.
Police said the suspect was wearing a hoodie and a mask.
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The car is believed to be a later model Toyota Corolla or Camry, tan in color.
Anyone with information is asked to call the Delano Police Department. The tip line number is (661) 721-3369.
After the shooting, police said they will move quickly to target gangs in the city through the holiday weekend.
The operation started on Friday afternoon.
"Two people dying is concerning," Nevarez said. "But in this case, the fact that we had two very young persons killed is especially tragic. As the police chief, I can promise you we'll be taking steps to find those responsible for this senseless tragedy."