Mast cells can be dispersed from human tonsils by a mechanical procedure or by the use of proteolytic enzymes. The latter procedure does not always increase cell yield and may adversely affect the mast cell response to secretory stimuli. Mechanically dispersed tonsillar mast cells secrete histamine in response to stimulation with anti-IgE and calcium ionophore A23187 by a calcium-dependent and energy-dependent mechanism. With compound 48/80 and basic polyamines, histamine release only occurs at cytotoxic concentrations. Functionally, human tonsillar mast cells are similar to adenoidal and lung mast cells.