Although Muhammad's preaching was basically religious, there was implicit in it a critique of the conduct and attitudes of the rich merchants of Mecca.

Attempts were made to get him to soften his criticism by offering him a fuller share in trade and a marriage alliance with one of the wealthiest families, but he decisively rejected such offers.

About 615 CE more active opposition from the Meccan’s began to surface. 

Points in the message of the Qur'an were questioned, such as the assertion that men would be resurrected before the Judgment.

Commercial pressure was brought to bear on Muhammad's supporters, and in some families there was mild persecution of junior members who followed him.

It is sometimes suggested that the main reason for opposition was the merchants' fear that the new religion would destroy the recognition of the Ka'bah as a sanctuary, but this is unlikely. Certainly attacks on idols appeared in the Qur'an, and Islam began to be characterized by the insistence that "there is no god but God" (Allah), but no attack was made on the Ka'bah, and the idols mentioned in the Quran had their chief shrines elsewhere.

A leader of the opposition arose in the person of Abu Jahl, a contemporary of Muhammad, who probably felt that the latter, despite his claim to be "only a warner" (of Judgment to come), was building a position of authority that might one day make him politically supreme in Mecca.  Many  Arabs deeply respected the kind of wisdom or knowledge that Muhammad was proclaiming.

In about 616 CE Abu Jahl organized a boycott of the clan of Hashim by the chief clans of Mecca, allegedly because the clan continued to protect Muhammad and did not curb his preaching; but, since few of the clan were Muslims, other questions may have been involved.

After three years the boycott lost momentum, mainly perhaps because some of the participants found they were harming their own economic interests. 

Both Muhammad's wife, Khadijah, and his uncle Abu Talib died in about 619, and another uncle, Abu Lahab, succeeded as head of the clan of Hashim.

Abu Lahab was closer to the richest merchants, and at their instigation he withdrew the protection of the clan from Muhammad.

This meant that Muhammad could openly be attacked and therefore could no longer easily propagate his new religion in Mecca.

He left for the neighboring town of at-Ta'if, but the inhabitants were insufficiently prepared to receive his message, and he failed to find support.

Having secured the protection of the head of another clan, he returned to Mecca.

In 620 CE Muhammad began negotiations with clans in Medina, leading to his emigration, Hegira or hijrah (flight or emigration), there in 622 CE.

It is difficult to assess the nature and extent of the persecution of the Muslims in Mecca.

There was little physical violence, and that almost always within the family or clan.

Muhammad suffered from some minor annoyances, such as having filth deposited outside his door.

The persecution is said to have led to the emigration of some of the Muslims to Ethiopia about 615 CE, but they may have been seeking opportunities for trade or military support for Muhammad. Some remained until 628 CE, long after Muhammad was established in Medina.

Whatever the nature of the persecution, the Muslims nurtured a long standing bitter over it.