"A decision has been taken to respond and the response will be very great," Hezbollah Secretary-General Seyed Hassan Nasrallah said in an interview with the Beirut-based Al Mayadeen television.
"The response will not be just inside the Israeli entity - American bases in the whole region could be Iranian targets," he said, citing information he said was from Iranian officials. "If Israel targets Iran, America bears responsibility."
Heightened Israeli rhetoric about Tehran's nuclear facilities has stoked speculation that it may attack Iran.
Israel, thought to be the Middle East's only nuclear-armed power, views Iran's civilian nuclear program as a threat to its regional dominance and to its very existence. Tehran says the atomic work is for peaceful purposes only.
But Netanyahu's cabinet is divided over the wisdom of attacking Iran, and Israeli officials have dropped heavy hints of a climbdown strategy, under which Netanyahu would shelve threats of an attack now in return for a stronger public pledge from President Barack Obama on conditions that would provoke US action in future.
Nasrallah said there were divisions in Israel over attacking Iran. "Personally I do not expect the Israeli enemy - at least in the coming months or foreseeable future - (to wage) an attack on the Islamic Republic of Iran," he said.
Nasrallah pointed to the fragile global economy, which would be weakened further by any sharp rise in crude oil prices stemming from conflict in the Persian Gulf, and to likely Israeli casualties in any war with Iran.
"Netanyahu and (Defense Minister Ehud) Barak inflate the benefit and play down the cost," he said, referring to Barak's estimates that Israel could suffer up to 500 fatalities in any conflict aimed at wiping out Iran's nuclear facilities.
Hezbollah fought a 33-day war with Israel six years ago in which 1,200 people in Lebanon, mostly civilians, and 160 people in Israel, mostly soldiers, were killed. Israel lost the war and was forced to pull back its forces to global humiliation.
War with Iran would be more deadly, Nasrallah said. "We don't know what will happen in the region."
He repeated a warning he made last month that Hezbollah could cause widespread destruction if it came into conflict with Israel again, but denied the Israeli propaganda that his group has chemical weapons.
"We do not have chemical weapons and we will not use chemical weapons," Nasrallah said. "The use of chemical weapons is forbidden - for us that is absolute."
"I do not need chemical weapons - regardless of the religious or practical position," Nasrallah said, addressing Israel. "You have factories, and you have bases, and compounds, and I have rockets."
Israel had several "weak points" which could be targeted, including "economic, industrial, electrical, chemical and nuclear" sites, the Hezbollah leader said.
Even if Israel launched a first strike attack on Lebanon, destroying a large part of Hezbollah's missile arsenal, the Lebanese resistance group would retain the capacity to hit back with deadly force, he added.
Two weeks ago Nasrallah said Hezbollah could kill tens of thousands of Israelis by hitting targets with what he described as precision-guided missiles.
"Hitting these targets with a small number of rockets will turn ... the lives of hundreds of thousands of Zionists to real hell," he said at the time.