The gene product of the steel locus is a growth factor for mast cells and a ligand for the c-kit proto-oncogene receptor, a member of the tyrosine kinase receptor class of oncogenes. We studied the effect of recombinant human c-kit receptor ligand stem cell factor (rhSCF) on the release of preformed (histamine) and de novo synthesized mediators [prostaglandin D2 (PGD2) and peptide leukotriene C4 (LTC4)] from mast cells purified from human lung parenchyma (HLMC). rhSCF (0.01-10 ng/ml) concentration-dependently induced histamine release from HLMC. rhSCF also induced the de novo synthesis of PGD2, whereas it did not induce the release of LTC4. The release of mediators from HLMC caused by rhSCF was extremely rapid, and was Ca2+- and temperature-dependent.