In vivo microdialysis was used to investigate the effects of an IP injection of diazepam or buspirone (each at 3 mg/kg) on spontaneous efflux of noradrenaline in rat frontal cortex, and on changes in efflux induced by naturalistic stress. After drug administration, rats either remained in their home cages or were transferred individually to a novel cage, 1 h later. The novel cage was brightly lit (1500 lux) and contained another, unfamiliar rat. After transfer to the novel cage, noradrenaline efflux was lower in diazepam-injected rats than in their vehicle-injected counterparts. However, in both cases, stress caused a significant increase in efflux and the net increase was not affected by diazepam. Similarly, buspirone, which increased spontaneous efflux of noradrenaline, did not affect the net increase in efflux during stress. Neither compound modified locomotor activity in the novel cage. This suggests that any changes in noradrenaline efflux are unrelated to drug effects on non-specific arousal. It is concluded that generically unrelated anxiolytic agents can have different effects on spontaneous efflux of noradrenaline but do not modify the noradrenergic response to naturalistic stimuli.