OBJECTIVE To evaluate whether MgSO4 solution administered IV would improve the clinical signs and lung function of horses with severe asthma and potentiate the effects of salbutamol inhalation in those horses. ANIMALS 6 adult horses with severe asthma. PROCEDURES Asthmatic horses were used in 3 crossover design experiments (6 treatments/horse). Clinical scores for nasal flaring and the abdominal component associated with breathing and lung function were determined before and after administration of salbutamol (800 μg, by inhalation), MgSO4 solution (2.2 mg/kg/min, IV, over 20 minutes), and combined MgSO4-salbutamol treatment. The data were collected during experimental procedures to assess salbutamol inhalation versus mock inhalation, MgSO4 infusion versus infusion of saline (NaCl) solution (adjusted to the same osmolarity as the MgSO4 solution), and the combined MgSO4-salbutamol treatment versus salbutamol inhalation alone. RESULTS Infusion of MgSO4 significantly improved clinical scores when administered alone or in combination with salbutamol inhalation. With the combination treatment, lung function improved, albeit not significantly. Tidal volume also increased following combined MgSO4-salbutamol treatment. Salbutamol alone significantly improved lung function, whereas saline solution administration and a mock inhalation procedure had no effect on the studied variables. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that MgSO4 infusion alone or in combination with salbutamol inhalation improved the clinical signs of severely asthmatic horses. The effects of MgSO4 were not associated with significant lung function improvement, which suggested that the changes observed were attributable to alterations in the horses' breathing patterns. Infusion of MgSO4 solution at the studied dose offers little advantage over currently used medications for the treatment of severe equine asthma.