Lead was administered to adult male rabbits in drinking water at a 0.1% concentration for four and five week periods. The lead contents were determined in the central and peripheral nervous tissues and in the liver, kidney, and intestinal mucosa. The conduction velocity of sciatic nerve and the activities of drug metabolizing enzymes in other tissues were determined. The lead concentration in the blood was at a steady state at four to five weeks of exposure. Lead accumulated in all tissues except the brain. The brain lead concentration was 40 to 50% of that in the blood, indicating the existence of a blood-brain barrier. However, the lead concentration in the sciatic nerve increased significantly from four to five weeks of exposure and exceeded that in the blood. This indicates the lack of a blood-nervous tissue barrier in the sciatic nerve allowing a continuous accumulation of lead. This accumulation affected the function of the sciatic nerve; motor nerve conduction velocity decreased from the control level (58.3 +/- 7.4 m/sec) to 43.8 +/- 6.3 m/sec after the four-week exposure and to 35.0 +/- 1.3 m/sec at 5 weeks of exposure. After five weeks of exposure, no changes in the hepatic, intestinal, or renal drug metabolizing enzyme activities were found. These results suggest that motor nerve conduction velocity is affected by lead exposure prior to any influence on biotransformation enzymes.