"Thanks be to Allah, 43 apostates were killed and around 30 were wounded in an attack carried out by Islamic State soldiers on a bus transporting Shiite Ismaili infidels in the city of Karachi," the extremist group said in a statement posted on jihadist Twitter accounts.
It was the first official claim of responsibility by the IS leadership of an attack in the Afghanistan-Pakistan region.
IS, which has seized control of large parts of Syria and Iraq, announced in January the creation of a branch in what it called "Khorasan province", encompassing Afghanistan, Pakistan and parts of surrounding countries.
Gunmen on motorcycles boarded a bus and opened fire on commuters this morning, in the latest attack directed against religious minorities this year.
The pink bus was pockmarked with bullet holes and blood saturated the seats and dripped out of the doors on to the concrete.
"As the gunmen climbed on to the bus, one of them shouted, 'Kill them all!' Then they started indiscriminately firing at everyone they saw," a wounded woman told a television channel by phone.
At least 43 people had been killed and 13 wounded, provincial police chief Ghulam Haider Jamali told media.
Prime Minister Nawaz Sharif said he was saddened by the attack.
"This is a very patriotic and peaceful people who have always worked for the wellbeing of Pakistan," he said. "This is an attempt to spread divisions in the country."
English leaflets left in the bus were headlined "Advent of the Islamic State!" and used a derogatory Arabic word for Shi'ites, blaming them for "barbaric atrocities ... in the Levant, Iraq and Yemen".
The leaflets also blamed Shi'ites for a deadly sectarian attack in Rawalpindi, next to the capital Islamabad, and raged against extrajudicial killings by police.
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