Pharmacokinetics and pharmacodynamics of metoprolol, a selective beta-l blocker, were examined for 360 minutes after intravenous bolus administration of metoprolol to 6 dogs. Plasma concentration and excreted amount in the urine metoprolol were measured by liquid chromatography with fluorescence detection. PR interval and heart rate were measured by ECG monitoring. Blood pressure was monitored through intraarterial catheter in femoral artery and cardiac output by thermodilution method using Swan-Ganz catheter. To analyze the effect site concentration-response relationship, plasma concentration and pharmacological effects were simultaneously fitted to a two pharmacokinetic compartment linked to pharmacodynamic model with NONLIN program. Results are as follows. 1) The plasma concentration of metoprolol after intrvenous injection decreased biexponentially. The terminal half-life estimated was 1.33 ± 0.40 hours and the volume of distribution at steady state (Vdss) and the total body clearance were 1.04 ± 0.4 L/kg, 6.55 ± 2.21 L/hr, respectively. The central compartment volume of distribution and peripheral compartment volume of distribution were 0.35 ± 0.14L/kg and 0.69 ± 0.34L/kg. The renal clearance and intercompartment clearance were 0.53 ± 0.25 L/min and 0.35 ± 0.19 L/min. 2) Simulated biophase concentration-response curve shows hyperbolic relationship and the estimated concentration-effect relationship was best explained by Emax model when the prolongation of PR interval and the reduction of the heart rate were used as pharmacodynamic parameters. Emax and EC50 were estimated to be 26.3 ± 4.7 msec and 88.8 ± 82.3 g/ml for PR interval, and 48.7 ± 18.8 beats/min and 113.5 ± 78.7 ng/ml for heart rate, respectively. 3) The changes of cardiac output-effect site concentration relationship was best fitted by a linear model and the slope of the relationship was 0.005 ± 0.003. Diastolic blood pressure-effect site concentration relationship was also explained by the linear model and the slope of the relationship was 0.038 ± 0.034.