A newly developed microdialysis probe for measurement of drugs in unrestrained, conscious animals was used for quantitation of antipyrine in liver and blood of rats. Microdialysis probe were implanted in the liver and right jugular vein of rats; antipyrine was then administered at a dose of 50 mg/kg i.p. The concentration of antipyrine was determined in the fluid from the two probes and compared with measurement made on blood drawn from the left jugular vein. The elimination half lives in serum, blood dialysate and hepatic dialysate were 2.24 +/- 0.09, 2.06 +/- 0.31 and 2.10 +/- 0.32 hrs, respectively; there were not significantly different statistically. The concentration of Na+, K+ and Cl- in the hepatic dialysate was stable at least for up to 12 hrs in anesthetized rats. In unrestrained, conscious animals these electrolytes were stable in hepatic dialysate for at least 48 hrs. Therefore, the microprobe should be useful for analysis of drugs in extra cellular fluids of rats liver for up to 48 hrs. These studies suggest that this microdialysis technique by employing the newly developed probe will be useful in many studies on pharmacokinetics and drug metabolism in the organ.