"The army is treating it as a grave incident," Lt. Col. Avital Leibovitch told reporters in a telephone briefing.
Two men and two women, one pregnant, were killed in the drive-by shooting on a busy highway in the occupied Palestinian territory used by Palestinians and occupiers.
"Security was stable for the past few years and we hope this will not cause any deterioration," Leibovitch said. An Israeli minister also said he hoped the attack would not derail the talks.
Israeli forces in the West Bank were treating it as a grave incident and were searching for the perpetrators, Leibovitch said. She could not say how many shots were fired at the vehicle.
The attack occurred after dark near the flashpoint West Bank city of Hebron, where Israeli occupiers live among Palestinian residents.
No group claimed responsibility for the attack. But Hamas, which controls the Gaza Strip, praised the killings. "Hamas praises the attack and regards it as a natural response to the crimes of the occupation," said Sami Abu Zuhri, a Hamas spokesman in Gaza.
Israeli police said the incident occurred near the Kiryat Arba settlement. Israel's Channel Two television said they had been shot from a passing vehicle.
Defense Minister Ehud Barak promised in a statement that Israel would "exact a price" from those who shot dead the Israelis. "This is an apparent attempt by lowly terrorists to sabotage the attempt to achieve a diplomatic process and to try to hurt the chances of the talks opening in Washington" this week, Barak added in a statement.
