The effects of diazepam quipazine, lysergic acid diethylamide (LSD), and 2,5-dimethoxy-4-methylamphetamine (DOM) were examined on a conditioned suppression paradigm. Food-deprived rats were trained to drink a liquid diet from a tube. Subsequently, intermittent 7-s tones were presented during the daily 10-min sessions, the tube being electrified during the last 5 s of each tone. The subject gradually learned to suppress contact with the tube during the tone periods to a low stable level (punished responding) and consumed stable volumes of the liquid diet during the silent periods (unpunished responding). Treatment with diazepam caused large increases (1,000% of control) in punished responding. The hallucinogens produced only modest increases (200–300%), while quipazine did not significantly increase punished responding. Metergoline pretreatment (0.1–2.0 mg/kg, 180 min) had no effect on punished responding itself, and there was no significant alteration of the diazepam dose-response pattern. The weak increase in punished responding by LSD was antagonized by metergoline, but the interaction between metergoline and DOM was variable and inconsistent. Diazepam, quipazine, LSD, and DOM caused dose-dependent decreases in unpunished responding (fluid intake). Metergoline alone decreased unpunished responding only at 2.0 mg/kg. Metergoline pretreatment (1.0 mg/kg) only slightly antagonized the LSD effect on unpunished behavior, but shifted the dose-response curves of DOM and quipazine for decrease in fluid intake to the right approximately eight fold. On the contrary, the dose-response curve of diazepam to decrease fluid intake was shifted to the left by metergoline pretreatment. These data suggest that altered activity of brain serotonin (5-HT) neurons is not responsible for the dramatic increase in punished responding by diazepam. The hallucinogens, quipazine, and diazepam all produce a decrease in unpunished responding, but they appear to do so by different neuropharmacological mechanisms. In addition, there may be at least slight differences in the mechanism by which LSD produces its effects as compared with that of quipazine and DOM.