The present study was designed to examine the disruptive effects of reinforcement during stimulus onset/offset in drug‐discrimination tasks. Rats were trained on a two‐lever task to discriminate either pentylenetetrazole (PTZ, 20 mg/kg) or cocaine (CN, 10 mg/kg) from saline, with food used as a reinforcer. Tests for onset of the drug stimulus were conducted immediately after an i.p. injection of the training stimulus. In order to test drug offset, rats trained to discriminate PTZ were tested immediately after an injection of diazepam (DZP, 5 mg/kg) given 15 min after an injection of PTZ. Responses on either lever were reinforced throughout the 20‐min session. Although the onset or offset of a drug stimulus significantly changed lever selection, consistent change in lever selection was obtained from approximately 30% of the subjects. For both the CN and PTZ onset groups, lever changing occurred after either (1) a disruption in responding, which produced a period of no reinforcement, or (2) very early in the session, which provided only brief exposure to reinforcement for responding on the other lever. Drug‐induced disruption of behavior was much more apparent during PTZ onset than during CN onset. For animals that continued to be reinforced for nondrug responding after onset of the drug stimulus, discrimination of the training stimulus during subsequent training was not disrupted by the testing procedure.