The toxic effects of nanoparticles (NPs) of ZnO and CuO to particle-ingesting model organism protozoa Tetrahymena thermophila were evaluated. Nano-ZnO was remarkably more toxic than nano-CuO (EC50 values ∼5mgmetal/l versus 128mgmetal/l). Toxic effect of CuO depended on particle size: nano-CuOwas about 10–20 times more toxic than bulk CuO. However, when calculated on basis of bioavailable copper (quantified using recombinant Cu-sensor bacteria) the 4-h EC50 values of nano- and bulk formulations were comparable (2.7 and 1.9mg bioavailable Cu/l, respectively), and statistically different from the EC50 value of Cu2+ (1.1 mg/l). Differently from CuO particles, bulk and nanosized ZnO as well as Zn2+ were of similar toxicity (4-h EC50 values 3.7 and 3.9mg bioavailable Zn/l, respectively, and 4.9mg Zn2+/l). Thus, the toxic effect of both, CuO and ZnO (nano)particles to protozoawas caused by their solubilised fraction. The toxic effects of the copper compounds were not dependent on exposure time (4 and 24 h), whereas the toxicity of zinc compounds was about 1.5 times lower after 24 h of exposure than after 4 h, probably due to adaptation. In summary, we recommend T. thermophila as a simple eukaryotic particle-ingesting model organism for the toxicity screening of NPs. For the high throughput testing we suggest to use the 4-h assay on microplates using ATP and/or propidium iodide for the evaluation of cell viability.