Histamine release from purified rat peritoneal mast cells (PMC) was examined and compared to that from a non-purified preparation (PEG). Both PEC and PMC released similar amounts of histamine upon stimulation with compound 48/80, calcium ionophore A23187 and substance P. In contrast, IgE-dependent histamine release from PMC caused by antigen, anti-IgE and concanavalin A was very low compared to that of PEC. The reduced IgE-dependent histamine release from PMC, however, was recovered when PMC was reconstituted with non-mast cells (NMC) present in the peritoneal cavity. The effect was time-dependent and reached a plateau in 30 min. NMC from both sensitized and nonsensitized rats recovered the reduced histamine release from PMC dose-dependently. The potentiating effect of NMC was observed even in the presence of excess amount of phosphatidylserine. Supernatants of NMC and a mixture of PMC and NMC incubated for 1 hr at 37 degrees C, however, failed to potentiate the histamine release. These results demonstrate that IgE-dependent histamine release from rat peritoneal mast cells is upregulated by other cells present in the peritoneal cavity, and that the mechanism involved is distinct from that of phosphatidylserine.