The pharmaceuticals and pharmaceutical metabolites salicylic acid, paracetamol, clofibrinic acid, and methotrexate were examined with regard to their biological degradability and toxicity toward algae, Daphnia, fish embryos, luminescent bacteria, ciliates, and the fish cell line BF-2. The EC50 values calculated for the most sensitive organismic test (all except cell cultures) in each case were for salicylic acid, 37 mg/L (fish embryos); for paracetamol, 50 mg/L (Daphnia); for clofibrinic acid, 86 mg/L (fish embryos); and for methotrexate, 45 mg/L (ciliates). However, in the case of paracetamol, clofibrinic acid, and methotrexate, the fish cell line BF-2 reacted even more sensitively with EC50 values of 19 mg/L (paracetamol), 14 mg/L (clofibrinic acid), and 3 mg/L (methotrexate). Salicylic acid and paracetamol proved to be easily degradable. The predicted exposure concentration calculated according to the procedure of the EU Draft Phase I for new pharmaceuticals (CEC III/5504/94, draft 4) was based on the total estimated quantity of these substances consumed and indicated that their entry into the environment is theoretically possible. These results show that (1) the four tested pharmaceuticals may be present in the environment, (2) the substances led to effects in at least one ecotoxicological test, and (3) the most sensitive reactions were observed for a nonstandard test which incorporates relevant end points for the respective pharmaceuticals. This demonstrates that a limitation to the standard tests (algae, Daphnia, and fish) would have underestimated the toxicity of paracetamol, clofibrinic acid, and methotrexate. In addition to improved exposure estimates, the EU guideline should therefore contain a test strategy adapted to their modes of action, which permits the definite identification of pharmaceuticals with high ecotoxic potential, and consequently the appropriate provisions.