Airway hyperresponsiveness (AHR) to water-soluble cooling lubricants (CL) induced by aerosol administered by tracheal tube was studied in a rabbit model of occupational lung disease. Two commercial CL were examined: the first was of the boric acid amine ester type without biozide (CL-BAE), the second was of the sulfonate type with biozide (CL-SB). 50, 5.0 or 0.5 mg/m3 CL was administered over a period of twice 2 h to six different groups of rabbits. Airway responsiveness (AR) to aerosols of 0.2% and 2.0% acetylcholine solution (ACH) was measured before and after each exposure to CL. A control group A of nine animals not exposed to CL showed no significant respiratory responses following inhalation of 0.2% ACH for 1 min. Conversely, inhalation of 2.0% ACH almost doubled the dynamic elastance (Edyn) in the ACH challenge test in this animal group. Airway resistance (RI), Edyn, slope of inspiratory pressure generation (ΔPes/tI), arterial pressure (Pa) and arterial blood gas tensions (PaO2, PaCO2) were not significantly altered during and after exposures to CL. However, after CL-BAE inhalation of 50 and 5 mg/m3 over 4 h, the amplitude of the ACH-induced airway obstruction indicated by the changes in Edyn rose significantly to almost five times the control response before exposure (group C, D, p < 0.005). Similar changes in RI and ΔPes/tI were obtained. After inhalation of 0.5 mg/m3 CL-BAE (group D), no significant changes in AR were observed. Similar to CL-BAE inhalation of 50 mg/m3, CL-SB caused enlarged AR in the ACH challenge test (group E), whereas no significant changes were found after exposure to 5.0 and 0.5 mg/m3 in groups F and G. In summary, CL aerosols with and without biozide in the range of 50 and 5 mg/m3 applied via tracheal tubes increased AR to ACH within 4 h of exposure in a time- and concentration-dependent manner. It has to be assumed that this augmented AR indicates an increased risk of developing lubricant-induced obstructive lung diseases.