Rats treated with a single dose of triethyl lead chloride (TEL) by subcutaneous injection (7.9 mg/kg) showed a transient increase in latencies to lick the hind paw during hot-plate testing. The time course of triethyl lead-induced antinociception was temporally associated with depressed binding capacity of benzodiazepine receptor sites and reduced levels of Substance P. Both of these changes appeared to be confined to the hippocampus and were not apparent in the cortex or striatum of treated rats. Met-enkephalin levels were not altered in any region studied at any time during the 21-day postdosing period. Lead levels within the brain were higher than blood levels 1 week after triethyl lead injection. Although changes in more than one factor may account for the antinociceptive effect of triethyl lead, the hippocampus seems especially vulnerable to this amphiphilic organometal.