Quantitative structure–activity relationships (QSARs) have been developed with the logarithm of the inverse of 15-min toxicity (pT 15 ) toVibrio fischeri(the acute Microtox test). Statistically, robust QSARs were found for alkanones acting by the nonreactive, baseline narcosis mechanism of action [pT 15 =0.99(logK ow )−2.08,n=6,s=0.24,r 2 =0.988,F=405]; aldehydes acting by the Schiff base-forming mechanism of electrophilicity [pT 15 =0.55(logK ow )−0.58,n=6,s=0.07,r 2 = 0.994,F=782]; and alkenals acting by the Michael-type acceptor mechanism of electrophilicity [pT 15 =0.52(logK ow )+0.35,n=6,s=0.19,r 2 =0.914,F=54.5]. Efforts to model toxicity across mechanism of action resulted in the development of a response surface [pT 15 =0.79(logK ow )−1.17(E LUMO )−0.41,n=19,s=0.46,r 2 =0.892,F=75.3]. In addition, an excellent correlation was found betweenTetrahymena pyriformis[log(1/IGC 50 )] andV. fischeri. [log(1/IGC 50 )=0.86(pT 15 )−0.25,n=19,s=0.25,r 2 =0.957,F=405] toxicity.