ABSTRACT: Originally reported in 1983, channel catfish anemia (CCA), also ‘white lip’ or ‘no blood,’ is a major idiopathic disease affecting commercial production in the Mississippi Delta region of the USA. Affected individuals are characterized by lethargy, anorexia, extreme pallor, and packed cell volumes often below 5%, but a definitive cause for CCA remains elusive. Records from the National Warmwater Aquaculture Center (NWAC) reveal that, on average, CCA accounted for 4.7% of case submissions from 1994 to 2012. Known infectious agents, parasites, and perturbations in commonly measured water quality variables have been largely excluded, and research has focused on potential feed-related etiologies, particularly folic acid deficiency. No natural or anthropogenic contaminants have been found in feeds, and no associations have been made to any particular feed brand or formulation, or to the age or condition of the feed itself. Contrary to reports indicating a short clinical course, NWAC records indicate an insidious condition where certain ponds have contained fish diagnosed with CCA for up to 4 consecutive years and individual outbreaks have persisted for at least 5 mo. Investigation into the iron status of CCA-affected fish revealed values consistent with iron deficiency anemia, including low-packed cell volume (mean ± SE, 5.6 ± 1.0 vs. 24.8 ± 2.4%), serum iron (35.2 ± 3.5 vs. 104.4 ± 18.5 µg dl^-1), liver iron (12.2 ± 2.6 vs. 23.3 ± 4.6 µg g^-1), and percent transferrin saturation (14.5 ± 2.7 vs. 26.9 ± 3.1%) in anemic and healthy controls, respectively. Administration of parenteral iron produced complete recovery and returned iron indices to within the ranges of normal controls. Despite these findings, factors predisposing a state of hypoferremia remain unknown.