In the serious decline of European otters (Lutra lutra) over the last decades, polychlorinated biphenyls (PCBs) are considered to be one of the major factors. As no experiments can be conducted with otters, an eco-epidemiological study was performed to derive no observed effect concentrations (NOECs) for PCBs in the otter. A strong negative correlation was found between hepatic vitamin A and polychlorinated biphenyl (PCB) concentrations expressed as TCDD-equivalents (TEQs), coinciding with a higher incidence of infectious diseases. The no-effect concentration for vitamin A reduction was 2 ng TEQ/g lipid, 10-fold reduction was already found in animals with 5 ng TEQ/g lipid. The TEQ-levels measured with a reporter gene assay based on chemical-activated luciferase expression (the CALUX assay) correlated well with the TEQ levels calculated based on non- and mono-ortho PCB concentrations. The TEQ levels in blood and liver correlated well when expressed on a lipid basis. In living captive otters blood plasma TEQ levels (either measured based on gas chromatography (GC) or CALUX measurement) were lower than in the feral otters, and positively correlated with plasma total and free thyroid hormone but not with plasma retinol levels. Hepatic vitamin A concentration was found to be a physiologically relevant effect parameter. The NOEC for hepatic vitamin A reduction was translated into TEQ levels in fish and sediment. The CALUX response in 50-500 μl blood plasma proved to be a sensitive non-destructive biomarker for quantification of internal TEQ levels. Copyright (C) 1998 Elsevier Science B.V.