The highly selective 5-HT4 receptor antagonists, SB 204070A (0.001-0.1 mg/kg s.c., 30 min pretest) and SB 207266A (0.01, 1 and 10 mg/kg p.o., 1 hr pre-test), increased time spent in social interaction without affecting locomotor activity, in a rat 15 min social interaction test under high light, unfamiliar conditions. At 1 and 10 mg/kg s.c., SB 204070A was no longer active. These results are consistent with the profile expected of anxiolytic treatments in this procedure. In a rat 5 min elevated x-maze test, SB 204070A (0.01 and 1 mg/kg s.c., 30 min pre-test) significantly increased the percentage of time spent on the open arms. SB 204070A (0.01 mg/kg s.c.) and SB 207266A (1 mg/kg p.o., 1 hr pre-test) also increased percentage entries to the open arms. Neither compound affected locomotion at any dose tested in the procedure. The effects of both compounds in this procedure are also consistent with anxiolysis. Neither SB 204070A (0.1 or 1 mg/kg s.c., 30 min pre-test) nor SB 207266A (0.1 or 1 mg/kg p.o., 1 hr pre-test) affected either unpunished or punished responding, in a rat Geller-Seifter conflict model of anxiety. The maximal efficacy of both SB 204070A and SB 207266A in the rat social interaction test was similar to that of the benzodiazepine anxiolytic chlordiazepoxide (5 mg/kg s.c. or p.o.) used as a positive control, but was considerably less in the elevated x-maze procedure. The results suggest that 5-HT4 receptor antagonists may have modest anxiolytic-like actions in rats.