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Sixty-eight families of USDA303 channel catfish Ictalurus punctatus were evaluated for growth performance for 30 d. The fastest- and slowest-growing catfish families were further evaluated to examine the hypothesis that genes or gene products associated with the growth regulatory and stress axes can be used to describe differences in growth performance. Research examined mRNA levels of genes involved in the growth hormone–insulin-like growth factor (GH–IGF) network in fast- (family A) and slow-growing (family H) USDA303 catfish. Fish (59.0 ± 2.4 g) were fed for 7 weeks, weighed, and had tissues for RNA extraction. The remaining fish were subjected to an acute 10-min dewatering stress. Insulin-like growth factor-II mRNA was higher in the muscle of fast-growing fish, while the levels of IGF-I receptor (IGF-IR) and IGF-II receptor (IGF-II) were similar. Muscle IGF-IIR mRNA was two-fold higher than muscle IGF-IR mRNA. There were no differences in liver and muscle IGF-I and GH receptor mRNA or pituitary GH mRNA between the fastand slow-growing fish. Fast-growing fish consumed 135% more feed than slow-growing fish, though the abundances of ghrelin mRNA in the gut and neuropeptide Y mRNA in the hypothalamus were similar. Cortisol levels were negatively correlated to weight gain. These results suggest that the variation in growth between fast- and slow-growing USDA303 catfish is explained, in part, by the variation in the GH–IGF and stress axes. The relationship between cortisol and weight gain warrants further investigation for possible exploitation in our selective breeding program.