We measured the fluctuations in plasma pyridostigmine concentration from day to day on 3 consecutive days and hour to hour during 1 day in 11 myasthenic patients, by studying their usual dosage regime. Plasma pyridostigmine was measured by gas chromatography/mass spectrometry. The intraindividual day-to-day variation in plasma pyridostigmine levels was small. A highly significant relationship was found between the oral pyridostigmine dose and the area under the plasma concentration/time curve. The bioavailability of oral pyridostigmine was 3.6%, estimated by replacing one dose with an intravenous dose amounting to 1/30 of the oral dose. The relatively stable kinetic behavior of pyridostigmine is in contrast to the interpatient variability in dose requirement, indicating that monitoring of plasma pyridostigmine levels should be reserved for special cases.