Enzymatically dispersed human lung parenchymal cells were fractionated according to size by countercurrent centrifugation elutriation. Human lung mast cells eluted throughout the procedure indicating heterogeneity of mast cell diameters. In seven individual lung elutriations, the mean histamine content ranged from 2.5 +/- 0.5 pg/mast cell for the smallest diameter mast cells (8-10 microns) to 10 +/- 2.5 pg/mast cell for the largest (16-20 microns). Intermediate sized mast cells had correspondingly intermediate histamine contents. The maximum release of histamine after anti-IgE stimulation varied with mast cell size. Small mast cells consistently released less histamine (10 +/- 3.6% net) than the largest diameter mast cells (38 +/- 6% net). This differential histamine release could not be explained by cell surface IgE content which was similar in mast cells of all sizes. The concentration of anti-IgE for maximum histamine release was the same (2 micrograms/ml) for mast cells of all sizes. The generation of PGD2, the predominant cyclooxygenase metabolite of the human lung mast cell, also was correlated positively with mast cell size and to the quantity of histamine released. Studies to date indicate no clear pattern in agonist receptor activities as judged by the inhibition of histamine release by PgE2, the beta-adrenergic agonist, fenoterol, and adenosine. We conclude that human lung mast cells are heterogeneous with regard to size and function.