Mast cells are multifunctional, long-lived cells, widely distributed throughout vascularized tissues. Currently, more and more data indicate that mast cells are susceptible to HIV-1 infection at the progenitor stage of their ontogeny. Progenitor mast cells display expression of surface molecule CD4 as well as chemokine receptors, Le. CCR5 and CXCR4, prerequisite for HIV-1 cell entry. Interestingly, there are some factors, including certain cytokines and HIV-1 proteins, that modify surface molecule expression and, consequently, affect the mast cell susceptibility to HIV-1. HIV-1-infected progenitor mast cells are distributed to various tissues where mature and become HIV-1 resistant. However, mature mast cells retain the virus in latent form which might be reactivated via Toll-like receptor (TLR) stimulation or IgE cross-linking. Thus, mast cells could serve as a reservoir for HIV-1 replication and spread.