Rationale: Disturbances in respiration are common and debilitating features of Rett syndrome (RTT). A previous study showed that the 5-HT1a receptor agonist 8-OH-DPAT significantly reduced the incidence of apnea and the irregular breathing pattern in a mouse model of the disorder. 8-OH-DPAT, however, is not available for clinical practice. Sarizotan, a full 5-HT1a agonist, dopamine D2-like agonist/partial agonist has been used in clinical trials for the treatment of L-dopa induced dyskinesia. Objectives: To evaluate the effects of sarizotan on respiration and locomotion in mouse models of RTT. Methods: Studies were carried out in Bird and Jaenisch strains of methyl-CpG-binding protein 2 deficient heterozygous female and Jaenisch strain Mecp2 null male mice and in knock-in heterozygous females of a common nonsense mutation (R168X). Respiratory pattern was determined with body plethysmography and locomotion with open-field recording. Sarizotan or vehicle was administered 20 min prior to a 30 min recording of respiratory pattern or motor behavior. In separate studies, a crossover design was used to administer the drug for 7 and for 14 days. Measurements and Main Results: Sarizotan reduced the incidence of apnea in all three RTT mouse models to ~15% of their pre-treatment levels. In addition, the irregular breathing pattern was corrected to that of wild type (WT) littermates. When administered for 7 or 14 days apnea decreased to 25-33% of the incidence seen with vehicle. Conclusions: This study indicates that the clinically approved drug sarizotan is an effective treatment for respiratory disorders in mouse models of RTT. Word count: 248.