Hexafluorocyclobutene (HFCB), a cyclic analogue of perfluoroisobutene (PFIB), is a reactive gas that induces a fulminating pulmonary oedema in rats from which animals may die after an apparently asymptomatic period between 24 and 30 h, depending on the dose. To determine the dose of inhaled gas to the respiratory tract, the retention of HFCB has been determined in the rat at three inhaled concentrations with simultaneous measurement of respiratory parameters. Rats exposed continuously to HFCB retained 25%, 19% and 16% of the inhaled dose after exposure to 1.2, 6 and 30 ppm, respectively, which fell to 24%, 17% and 9% at 30 min and 21%, 16% and 6.5% after 1 h. The rate of uptake of HFCB decreased markedly at the highest concentration from 200 to 112 nmol min-1 kg-1 after 30 min and to 90 nmol min-1 kg-1 after a further 30 min. Ventilatory parameters were unchanged throughout the experiment and there was no evidence of pathological or histopathological damage at the end of the exposure. On renewal of exposure to gas after a 15-min pause, the percentage of gas retained was unchanged from that determined previously. The results indicate that there is a saturable component within the respiratory tract that is both time and concentration dependent. Hexafluorocyclobutene does not produce direct pathological damage outside the lung, which indicates that it may react rapidly with tissue components within the lung.