A simple and accurate method for measuring acetaminophen in serum was developed using liquid chromatography with electrochemical detection. Acetaminophen can be quantitated in 100 microliter of serum over the range of 20 ng/ml--20 microgram/ml. The method is linear (r = 0.9997) and reproducible (RSD = 3.0% at 2 microgram/ml, RSD = 5.1% at 200 ng/ml, n = 6). An internal standard (N-propionyl-p-aminophenol) is used, and a single extraction is performed.