The concentration ratios of parotid saliva to plasma lidocaine were determined in rats after a single dose (10 mg of lidocaine/kg) and constant infusion (60 micrograms of lidocaine/kg/min). Parotid saliva and plasma samples were obtained at 10, 20, and 30 min after single-dose lidocaine administration and at 70, 80, and 90 min after the initiation of a lidocaine infusion. The saliva/plasma concentration ratios for lidocaine after single-dose administration decreased from 1.13 +/- 0.03 at 10 min to 0.51 +/- 0.06 at 30 min, whereas the ratios determined during the lidocaine infusion remained constant (0.43 +/- 0.03, 0.45 +/- 0.03, and 0.43 +/- 0.04) over the time period tested. The variable saliva/plasma concentration ratios obtained after single-dose administration may be associated with rapid drug distribution between the plasma and peripheral compartments and variation in lidocaine binding to plasma proteins. However, during constant lidocaine infusion, a steady-state concentration was achieved within 70 min, as demonstrated by the constant saliva/plasma concentration ratios.