The effects on a fixed ratio-40 (FR-40) operant behavior of intracerebroventricular (ICV) administration of the hallucinogens lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-methylamphetamine (DOM), mescaline or the non-hallucinogenic LSD-analogue lisuride were compared with intraperitoneal (IP) administration. Infusion of LSD (8.5 to 34 micrograms) into the left lateral ventricle produced a dose-dependent decrease in reinforcers and an increase in 10-sec periods of non-responding (pause intervals). The time-course of LSD showed a shorter latency to onset after ICV than IP administration. The ED50 for doses increasing pause intervals by ICV administration was 15 micrograms. This disruption was greater than that produced by IP administration of equivalent doses of LSD (IP ED50: 19 micrograms). DOM (40 to 120 micrograms) infused into the lateral ventricle also produced a dose-dependent disruption of FR-40 behavior. ICV DOM also showed a rapid onset to peak effects, but a slower offset than LSD, and was 3 times more potent than systemic administration (ED50s: 58 micrograms ICV vs. 153 micrograms IP). Mescaline was much more potent in disrupting FR-40 behavior by the ICV route than by IP administration. The ICV ED50 for doses of mescaline increasing pause intervals was 74 micrograms, in contrast to an ED50 following systemic administration of 2251 micrograms, demonstrating a 30-fold difference in potency. Lisuride administered via the ICV route was no more potent than by IP administration with ED50s of 4 micrograms ICV and 4 micrograms IP. Lower doses of lisuride administered by both routes had a similar effect over time on pause intervals.(ABSTRACT TRUNCATED AT 250 WORDS)