A unified method is presented to derive maximum permissible concentrations (MPCs) of xenobiotic and naturally occurring substances. The method relies upon risk limitation expressed as the maximum potentially affected fraction of all possible species (PAFmax) in a component ecosystem, due to a bioavailable concentration of the considered substance. For xenobiotic compounds the method is simplified to the "HC5 approach," i.e., the MPC equals the hazardous concentration at which 5% of the species are unprotected. If the natural background of a substance is (partly) bioavailable, the related background effect, also expressed as PAF, is taken into account in deriving a MPC. Examples are given and MPCs for zinc, chromium, cadmium, copper, and lead for different levels of bioavailability in water are developed.