The possibility that Pb could affect benzene metabolism through inhibition of enzyme synthesis, was examined by studies of the effects of chronic oral Pb treatments on benzene conversion to phenol. Rats were given either distilled deionized water or 0.05, 0.58, 17 or 352 ppm Pb solutions as drinking water. After 6, 9, 12, and 15 wk of treatment, rats from each group were sacrificed and in vitro benzene metabolism by benzene hydroxylase was measured in liver enzyme preparations. After 24 wk, the remaining animals were injected ip with 400 mg/kg benzene and urinary phenol levels measured daily for 4 d. The enzyme activity, studied in vitro, was significantly increased in animals that ingested the 352 ppm solution for 6 wk. Also, Pb levels in all groups of animals were significantly higher in tissues from animals that ingested 352 ppm Pb. Although urinary phenol lvels accounted for 30-40% of the ip benzene dose, Pb ingestion had no significant effect on phenol excretion. These results suggested that oral Pb treatments had a significant effect on the enzyme responsible for benzene hydroxylation to phenol. However, unknown factors appear to compensate for these changes in vivo.