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Several indices of ventilatory heterogeneity can be identified from the volumetric capnogram and its graphic presentation, the single-breath diagram for CO2 (SBD-CO2). Physiologically based indices of pulmonary function (VTE, VCO2, FACO2, VDBohr, VDBohr%, VD/VTE, A1/A2) were calculated for healthy horses (group I, n = 5) and for horses with subclinical (group II, n = 7) or clinically manifest chronic obstructive pulmonary disease (COPD) (group III, n = 8) during tidal breathing and after medication with lobelin hydrochloride (Lobelin). We investigated the variability and repeatability of the lung function indices in healthy horses and in those with COPD both during tidal breathing and after administration of Lobelin, a centrally acting respiratory stimulant. In particular, we were interested in whether the discriminating ability of SBD-CO2-derived lung function indices would be increased between different patient groups after administration of Lobelin compared to those for the resting values. Of the indices studied, VTE, FACO2, VDBohr% and A1/A2 appeared to be those with good to excellent repeatability in discriminating healthy horses from those with COPD. Stimulating respiration with Lobelin gave no advantage in the repeatability of the lung function indices or in differentiating between horses with different degrees of COPD.