Background: Dextromethorphan (DXM) is an over-the-counterantitussive agent commonly abused for its NMDA receptor antagonism and dissociative effects similar to phencyclidine and ketamine. DXM is found in multiple formulations, and is widely available as a hydrobromide salt (DXM HBr). The serum bromide elevation common to DXM HBr overdoses has previously been described as falsely elevating serum chloride. Tolerance and dependence have not previously been established in DXM users. Hypothesis: Chronic DXM HBr abuse and tolerance may lead to escalating doses. This tolerance may be demonstrated by a gradual increase in the spuriously elevated serum chloride. Methods: We describe an adult male who frequently presented to an urban academic emergency department (ED) following recurrent use of a single DXM HBr formulation. Initial serum chloride concentrations at each visit for DXM HBr ingestion were compared over time via linear correlation. Results: Twenty-eight visits were included over 62 months from the first ED presentation. Chloride concentrations were available for 23 of those visits. Chloride concentrations ranged from 104 to 126 mmol/L. Correlation using chloride (y-axis) and months from first ED visit (x-axis) revealed R2=0.6321 (p<0.001); slope=0.238; standard error of the slope=0.041 (for every increase in month number, there was an increase in chloride of 0.238± 0.041 mmol/L). Discussion: Linear correlation indicates an increase in measured serum chloride that is unlikely due to chance alone, in the setting of recurrent DXM HBr abuse. These results suggest the development of tolerance and a need for escalated doses of DXM HBr. The patient confirmed a subjective need to escalate his dosing over the 5-year study period. This laboratory phenomenon has face validity but has not previously been evaluated from a laboratory standpoint. This patient experience is compelling both in theory and by statistical evaluation, but further study with similar assessment of many chronic DXM-abusing patients could establish a clearer link between abuse and tolerance. Conclusion: Over a 5-year period, this patient’s serum chloride (i.e., bromide) concentration demonstrated a gradual increase, suggesting the development of physical tolerance.