The authors studied the effect of chronic amantadine ingestion on its own disposition and that of acetaminophen in five healthy young adults. The half‐life of amantadine after 42 days ingestion was 15.1 ± 2.3 hours and was not different from 14.8 ± 4.4 hours after an acute ingestion (mean ± SD). However, chronic amantadine ingestion was associated with an increased apparent volume of distribution for acetaminophen, 1.1 ± 0.1 L/kg compared with 0.9 ±0.1 L/kg, when the two drugs were concurrently ingested after a 2‐week washout period. This difference in kinetic distribution was not reflected in terminal acetaminophen half‐life, 149 ± 54 versus 151 ± 55 minutes for chronic and acute amantadine ingestion, respectively. Plasma acetaminophen clearance with chronic amantadine ingestion (5.8 ± 2.6 mL/min/kg) was not different from that determined after acute coingestion of both drugs (4.3 ± 1.1 mL/min/kg). Thus, no change in recommended dose is necessary when these two drugs