The relevance of apoptosis to killing of intracellular Mycobacterium tuberculosis was studied with phorbol-differentiated THP-1 cells. Microparticles containing isoniazid and rifabutin induced intrinsic apoptosis and bacterial killing equivalent to that with dissolved drugs and maximally enhanced purinergic P2 receptor activity, while drug-free microparticles induced apoptosis via a different mechanism without killing bacteria.