A set of 25 substituted phenols have been examined in a QSAR study of their toxicity to fathead minnows, Pimephales promelas. The acute toxicities were measured in a flow-through system over a 96 hr. period as lethal concentration to kill 50 percent of the population, LC50. The negative logarithm of the toxicity, pLC50, which ranged over three orders of magnitude from 3.21 to 6.20, is correlated with molecular connectivity indexes. The best correlation was found with the simple index (1) chi and the valence index (3) chi rho with r=0.934 and s=0.296. The study includes an analysis of the stability of the regression model with respect to selection of the data set as well as the reliability of the model as compared to chance correlations. The structural interpretation of the regression model is also discussed. (Copyright (c) Bull. Environ. Contam. Toxicol. January 1984.)