Polyamidoamine (PAMAM) dendrimers of generation 6-4, G-5 and G-6 were evaluated for their aquatic toxicity using the test models Vibrio fischeri, Daphnia magna, Thamnocephalus platyurus, and two fish cell lines. Physico-chemical characterization of the particles in each of the different test media was performed. A significant eco- and cytotoxicological response was recorded at concentrations from 0.129 microM (7.4 mg L(-1)) to 16.30 microM (231.5 mg L(-1)). Daphnia magna was found to be the most sensitive test model, the RTG-2 fish cell line the least. The toxicological response correlated well with the dendrimer generation and therefore with the particle surface area, increasing surface area leading to increased toxic response. The response also correlated well with changes to the 4 potential in the different media, rather than the actual 4 potential, indicating a potential contribution of changes to the effective composition of the medium. For the cell lines, although spectroscopic studies indicated an interaction with the serum supplement, trends for this interaction do not correlate to those observed for the toxic response. The clear correlations of the observed toxicresponse with themeasured physicochemical properties pointtoward underlying structure activity relationships.