Acute intermittent hypoxia (AIH) elicits spinal synaptic plasticity, and is a simple, safe and effective (preliminary) way to facilitate respiratory function in people with amyotrophic lateral sclerosis (ALS). Since AIH involves brief reductions in the oxygen content of inspired air separated by periods of normoxia, participants experience a brief, modest oxygen desaturation. It is not known if AIH also leads to plasticity of autonomic nervous system function in people with ALS. Prior research suggests that heart rate variability (HRV) may be reduced in those with ALS. The fundamental aim of this project was to evaluate changes in HRV of adults with ALS, and test whether AIH affects HRV. ALS (n=17) and control participants (n=13) with predicted vital capacities >60%, underwent two sessions of AIH (15 cycles: 1min of 10%O2, 2min of 21%O2) and sham AIH (45min of 21% O2), presented in random order and separated by at least one week. The beat-to-beat standard deviation (SDRR), root mean square of successive differences in beats (RMSSD), low-frequency power (LF, nu), high-frequency power (HF, nu), and LF/HF Ratio measurements were used to analyze HRV. HRV was analyzed during baseline conditions before intervention, and 60 minutes post-intervention. Consistent with prior research, the RMSSD trended lower in patients (p=0.096). However, AIH had no discernible effect on HRV. We observed a two-way time-group interaction for LF/HF, where control participants in the pre-AIH condition had lower LF/HF than all other conditions, but the biological significance of this finding is unclear. These preliminary findings suggest that any AIH-induced motor plasticity occurred without triggering a detectable change in HRV. The study is still ongoing and requires additional subject recruitment to verify results.