Abstract Based on previous data from elevated plus-maze tests suggesting a possible anxiogenic effect of the insecticide chlorpyrifos (CPF), the experiment reported here was designed to determine whether this organophosphate (OP) caused an interoceptive discriminative stimulus (IDS) in rats similar to that produced by the anxiogenic drug pentylenetetrazol (PTZ). Rats were trained to discriminate PTZ (20 mg/kg) from saline, using a drug discrimination procedure. When appropriate lever selection was achieved, generalization tests were performed. Tests of various doses of PTZ showed that the drug exerts dose-dependent discriminative control over response. Two more generalization tests were conducted with 250 mg/kg of CPF and 76.8 mg/kg of LiCl for up to 9 days. Results revealed that CPF (250 mg/kg s.c.) produced a PTZ-like IDS that fully substituted for PTZ 24 h after injection and that subjective effects remain for at least 6 days. However, administration of LiCl did not produce any generalization to PTZ on any of the days tested. These results suggest that CPF shares a site of action, and perhaps functional properties, with PTZ that last for several days, are not due to general malaise and should be taken into account in the use of cholinesterase inhibitors in the treatment of different types of dementia.