A continuous marine fish cell line RSBF (i.e. Red Sea Bream Fin) w as utilized to screen the cytotoxicity and genotoxicity of polyethylenimine (PEI) and nickel chloride (NiCl2) in this study on the deleterious effects of aquatic genotoxins on fish. At the 0.01 to 1 μg/ml concentration tested, PEI had acute toxicity to the treated RSBF cells (IC50 =1.12, 0.92, 0.88 and 0.64 μg/ml PEI for time 0 h, 24 h, 48 h and 72 h after treatment, respectively ) and markedly inhibited their proliferation in a dose-dependent manner. At the 0.001 to 5 μ mol/L concentration tested, NiCl2 posed no acute toxicity but significantly stimulated their growt h (107%-214% of control). Random amplified polymorphic DNA (RAPD) technique was used to detect the genotoxic effects of PEI and NiCl2 by comparing the RAPD banding patterns of t he control and treated cells. RAPD analysis indicated that at the concentrations tested, PEI w as more genotoxic than NiCl2 to RSBF cells; that there was a slight dose-dep endent response in the genotoxic effect of PEI but not NiCl2; and that RAPD technique might provide a sensitive, non -specific genotoxic endpoint. And the potent cytotoxicity and genotoxicity of PEI on fish cells sho wed that we should be cautious in utilizing it as gene vector in fish gene transfer and human gene therapy.