We present a refinement of our model describing the association between enzyme activity and histopathological lesions in the catfish, Sciades herzbergii from a polluted port. The fish were sampled from a port known to be contaminated with heavy metals and organic compounds and from a natural reserve in Sao Marcos Bay, Brazil. Two biomarkers, hepatic glutathione S-transferase (GST) activity and histopathological lesions, in gills and liver tissue were measured. The values for GST activity were modeled with the occurrence of branchial and hepatic lesions by fitting a third-order polynomial. Results from the mathematical model indicate that GST activity has a strong polynomial relationship with the occurrence of branchial and hepatic lesions in both wet and the dry seasons but only at the polluted port site. The model developed in this study indicates that branchial and hepatic lesions are initiated when GST activity reaches 2.17 mu mol min(-1) mg protein(-1). Beyond this limit, GST activity decreased to very low levels and irreversible histopathological lesions occurred. This mathematical model based on two biomarkers (histopathological lesions and enzyme activity) in catfish provides a realistic approach to analyze stress induced by contaminants.