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The dorsal periaqueductal grey matter (dPAG) and inferior colliculus (IC) have been implicated in the control of defence reactions. Electrical and chemical stimulation of these structures induces escape behaviour, usually accompanied by autonomic responses and decreased pain sensitivity. Recently, we presented evidence for an involvement of histamine in the generation and organization of such defensive reactions in the midbrain tectum. In this study we have used the open field test to assess the effects of microinjections of histamine (40 nmol), dimaprit (10 nmol) and ranitidine (50 nmol) into the midbrain tectum of rats. Dimaprit is an agonist and ranitidine an antagonist of H2 histamine receptors. Immediately after the injections the animals were tested in an open field for 60 min. In an additional groups of rats, dimaprit was injected 15 min before the microinjections of ranitidine into either the dPAG or the IC. The results show that whereas histamine preceded by saline did not cause any apparent behavioural changes, ranitidine led to a behavioural reaction, with clear signs of fear, which was blocked by previous injection of dimaprit. Injections of only dimaprit had no apparent effects. The present results suggest that H2 receptors may be involved in the control of defensive behaviour following activation of the neural substrates of fear in the dPAG and IC.