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The most significant charitable donation Warren Buffett has ever made is his $37 billion pledge to the Bill and Melinda Gates Foundation. This donation, originally pledged in 2006, will take effect upon his death, as he has directed in his will. Individual contributions from Buffett represent some of the largest single charity contributions in history.

His estate consists of Berkshire Hathaway stock that he plans on contributing directly to the foundation and cash that he is leaving for his heirs to keep invested in index funds. Buffett's contribution has given him profound influence in the Bill and Melinda Gates Foundation, and he maintains active involvement in the organization. Buffett has a strong interest in philanthropy and in solving global health and educational problems. This interest led him to actively promote the foundation and encourage others to contribute, especially those with high-value estates.

Warren Buffett's heirs will receive significantly smaller amounts of cash from the estate, and some Berkshire Hathaway stock. Buffett encourages his children to follow his own values, including work ethic and being active in philanthropy. Buffett believes the Bill and Melinda Gates Foundation effectively addresses problems of global inequity in access to health care and education, including significant contributions to help these resources reach the world's poorest women and children. Much of what the foundation does is directed toward these issues. The foundation provides grants to other organizations and does direct research work to develop solutions in addition to its financial contributions. To Buffett, this organization is a wise investment of his estate.

Ultimately, all of Buffet's shares will be donated through annual gifts, set to complete 10 years after the settling of his estate.

On July 16, 2018, Berkshire Hathaway released a press release announcing that Warren Buffett has donated roughly $3.4 billion of company stock to five charities, which is the billionaire's largest contribution yet. Buffett's 13th annual donation consisted of roughly 17.7 million Class B shares (BRK.B) of the company. Shares closed at $192 that same day. 

11,867 of the Class A shares (BRK.A) he held were converted into 17.8 million Class B shares. With this current donation, about 43% of Buffett's 2006 holdings have now been donated to five foundations. Donations were made to the Bill & Melinda Gates Foundation, Buffett's own foundation, named for his late first wife Susan, as well as charities run by his children.

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