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Halothane (H) is metabolically converted mainly to trifluoroacetic acid (TFA). Whilst in surgical anaesthesia the proportion metabolised has been determined at 15–20%, we found in long-term exposure of volunteers to environmental concentrations (8–50 ppm) a proportion of 60–70% (Dallmeier and Henschler, Arch.Pharmac.297, R 20; 1977). To elucidate the reason for this gap we initiated experiments with the isolated perfused rat liver by offering steady-state concentrations ranging from 13 to 3200 ppm (gas phase) via the oxygenator. The difference of H-concentrations before and after liver passage was taken as amount metabolised, liver function was checked by standard enzyme tests. Metabolization rate (in terms of nMole H·g−1 liver·min−1) increases from 0.36 (13 ppm H) to 16.5 (3200 ppm), corresponding to proportions of conversion of 97% and 15%, respectively. Lineweaver-Burk plot reveals a linear relationship between reciprocals of metabolization rate and H-concentration, half saturation of the rate limiting step being calculated at 600 ppm H (gas phase). The ratio of TFA formed to the amount H metabolised is close to unity at low concentration ranges, with a distinct tendency to decrease towards higher H concentrations. It is concluded that biomonitoring of TFA-levels in blood or urine can be taken representative of H load only in the range of very low H-concentrations.