Whereas large lesions of the superior colliculus in rats increase locomotor activity in the open field, bilateral collicular microinjections of muscimol (an agonist of the inhibitory neurotransmitter GABA) have been reported to reduce open-field activity. This difference might be due to muscimol's acting on a subpopulation of collicular neurones, or to some feature of the microinjection technique. The issue was investigated by observing open-field behaviour after reversible lesions produced by bilateral microinjections of the local anaesthetic procaine (10–300 μg in 0.5 μl) into midbrain sites. Injections of procaine into the superior colliculus produced effects similar to those reported after muscimol injections: both locomotor activity and other exploratory responses were suppressed, with the rats spending much of their time motionless in an alert posture. In contrast, animals with injections of procaine into the mesencephalic reticular formation (MRF) ventral to the superior colliculus resembled rats given large collicular lesions: they showed very striking increases in locomotor activity, while their rearing and exploratory head movements were reduced. It is suggested that in some experiments large collicular lesions may have increased locomotor activity in the open field because they invaded underlying MRF. However, it is also possible that in rodents the acute effects of collicular inactivation, as assessed by microinjection of muscimol or procaine, are different from the chronic effects that are observed in experiments with electrolytic or radiofrequency lesions.