The quantitative relationship between molecular connective index (MCI) and half-lethal dose (LC50) of organic chemicals to rainbow trout were investigated based on a set of the observed data of 212 chemicals. The results showed that it was difficult to develop a single MCI model, even with structural correction factors introduced. The quantitative structure-toxicity relationship of the chemicals, however, could be depicted using separated models for individual classes of chemicals. The adjusted coefficients of determination of the models are between 0.62 and 0.92, and the overall mean residual is 0.283 log-units. Chemicals with relatively large residuals above 0.5 log-units account for less than 12% of the chemicals studied. Among seven chemical classes, the largest mean residual was derived from the model for organophosphate (OP).