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Multidrug resistance (MDR) caused by human ABCB1 (P-glycoprotein /MDR1) is one of the major obstacles in chemotherapy.To circumvent MDR, we screened natural compounds using the human T-cell lymphoblast-like cell line CCRF-CEM and its MDR counterpart (CEM/ADR5000 cells).Four guanidine alkaloids from Pterogyne nitens (galegine, pterogynine, pterogynidine, nitensidine A) were found to exert toxicity against CCRF-CEM cells, whereas CEM/ADR5000 cells were resistant to these alkaloids.Cells expressing human ABCB1 also showed resistance against the cytotoxic guanidine alkaloids.These results suggest that the four guanidine alkaloids are substrates for human ABCB1.