The involvement of vitamin C as a cofactor in detoxication mechanisms of fish was investigated by feeding selected amounts of the vitamin in diets of fingerling channel catfish (Ictalurus punctatus) that were concurrently exposed to toxaphene, a widely used organochlorine insecticide in the Southeastern United States. Three groups of fish were exposed continuously to each of five toxaphene concentrations—37, 68, 106, 218, and 475 ng/liter—and fed a diet containing 63, 670, or 5,000 mg/kg of vitamin C. After 150 days of toxaphene exposure, backbone collagen was significantly decreased in most fish fed the diet containing 63 mg/kg of vitamin C. However, the toxaphene concentrations of 37 and 68 ng/liter did not cause this effect in fish fed the 670 mg/kg vitamin C diet, and only the 475 ng/liter concentration significantly depressed backbone collagen in fish fed the 5,000 mg/kg diet. Spinal deformities were common among fish fed low vitamin C diets, but the incidence decreased as dietary vitamin C increased. Vitamin C concentrations in the backbones of toxaphene‐exposed fish were significantly lower than in controls, which suggests that the insecticide caused a functional vitamin C deficiency in bone tissue. The reduction in mucous cell number in the skin and epidermal thickness was more evident in fish exposed to toxaphene and fed the lower two concentrations of dietary vitamin C. In most toxaphene exposures, diets containing 670 or 5,000 mg/kg of vitamin C significantly reduced whole‐body residues of toxaphene and increased the tolerance of fish to chronic effects of the insecticide on growth, bone development, and skin lesions.