Stachybocins A, B and C, novel endothelin (ET) receptor antagonists, were isolated from the culture filtrate of Stachybotrys sp. M6222. They were extracted with ethyl acetate and purified by alumina and silica gel column chromatographies. The molecular formulae were determined to be C52H70N2O10 (stachybocin A) and C52H70N2O11 (stachybocins B and C). NMR spectra suggested they consisted of spirobenzofuran and terpene units. They showed inhibitory activity on the binding of 125I-ET-1 to rat ETA, human ETA and human ETB receptors. Endothelin (ET) is a potent and long-lasting vasoconstrictor peptide involved in cardiovascular diseases, so ET receptor antagonists are potential candidates for treating such diseases. During screening for ET antagonists from microbial culture broths, stachybocins were found from Stachybotrys sp. M6222. This paper describes the taxonomy of the producing organism, its fermentation, as well as the isolation, physicochemical properties and biological properties of stachybocins A, B and C. Structural elucidation will be published in a succeeding paper.