Extraction of penicillin G with sulfoxide extractants, petroleum sulfoxide (PSO) and di-isooctyl sulfoxide (DISO) was researched systematically. Based on research of the extraction equilibrium of penicillin G, the suitable extraction and re-extraction conditions were determined, and then extraction cascade and bench-scale experiments were carried out. The performance of extraction systems composed of PSO and DISO, with sulfonated kerosene as the diluent, is superior to that of n-butyl acetate owing to the low solubility of these new extractants in water. Their consumption during the extraction process was lower, and the recovery step of extractants from aqueous raffinate was eliminated. (C) 2004 Society of Chemical Industry.