This work explores the possibilities of generalizing a variety of narcotic global quantitative structure-activity relationships used in aquatic toxicological studies. The models developed herein are based on the static ciliate (Tetrahymena pyriformis) population growth impairment (IGC 5 0 - 1 ) data. Results are compared with models previously developed with the flow-through fish (Pimephales promelas) mortality (LC 5 0 - 1 ) data. The modeling approach is an extension of a recently developed expert system coupled with the response-surface concept. The expert system characterizes the molecular domain of non-specifically acting chemicals, both for neutral and amine narcotics. Toxicity surface(s) are defined using hydrophobicity quantified by the log1-octanol/water partition coefficient (logK o w ) and orbital electrophilicity quantified by the energy of the lowest unoccupied molecular orbital (E L U M O ) as global molecular descriptors. The ciliate response surface models: log(IGC 5 0 - 1 )=1.50+0.68logK o w -0.13E L U M O ; n=411, R 2 =0.890 and log(IGC 5 0 - 1 )=1.80+0.68logK o w ; n=51, R 2 =0.854 for neutral and amine narcotics, respectively, compares favorably with the fish model. The fish and ciliates response-surfaces appear to be parallel as they significantly deviate only by their intercepts.