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 (EC(50) values approximately 5mg metal/l versus 128mg metal/l). Toxic effect of CuO depended on particle size: nano-CuO was 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 EC(50) values of nano- and bulk formulations were comparable (2.7 and 1.9mg bioavailable Cu/l, respectively), and statistically different from the EC(50) value of Cu(2+) (1.1mg/l). Differently from CuO particles, bulk and nanosized ZnO as well as Zn(2+) were of similar toxicity (4-h EC(50) values 3.7 and 3.9mg bioavailable Zn/l, respectively, and 4.9mg Zn(2+)/l). Thus, the toxic effect of both, CuO and ZnO (nano)particles to protozoa was caused by their solubilised fraction. The toxic effects of the copper compounds were not dependent on exposure time (4 and 24h), whereas the toxicity of zinc compounds was about 1.5 times lower after 24h of exposure than after 4h, 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.