The effects of lysergic acid diethylamide (LSD) on investigatory responses of rats in a novel holeboard were assessed in a series of experiments. LSD (40-160 ug/kg) altered the temporal distribution of 'nose-poke' responses during a 24-rain session; LSDtreated rats responded iess than controls initially, yet increased their response rates late in the session. This dose-dependent effect was not related to the time course of the drug's action nor to alterations in genera1 locomotor activity. Only partial tolerance was found after eight daily injections of !00 i~g/kg LSD. When handling stress was minimized by placing the animals in an anteroom for I0 min before starting the test, the distribution of responding was normal although the overall frequency was still reduced. Converse!y, vigorous handling potentiated the LSD effect. These results are interpreted as indicating an increased sensitivity of the LSD-treated rats to the stimuli associated with being handled and placed into the novel holeboard rather than a direct effect on investigatory tendencies. This LSD-induced potentiation of defensive responses appears to compete with the active exploration of the novel environment.