The effects of 8-OH-DPAT on locomotor activity have not yet been clearly defined. Tricklebank et al. (1984) and Dourish et al. (1985) provide evidence that 8-OH-DPAT increases activity, whereas Mittman and Geyer (1989). Hillegaart et al. (1989) and Carli et al. (1989) suggest that it is reduced by the drug. In the present study, the effects of 8-OH-DPAT on locomotor activity and rearing were examined in habituated and unhabituated mice and rats. The effects of the drug were followed for up to 2 h in the mouse and up to 4 h in the rat. In unhabituated mice and rats, doses of 0.1 mg/kg or more of 8-OH-DPAT blocked activity during the period post-injection when control levels of activity were highest. However, after about 60 min in mice and 150 min in the rat a marked hyperactivity was observed, which was followed by a period of increased rearing. In habituated mice this biphasic effect on locomotor activity was also observed, but there was no increase in rearing. In habituated rats there was no decrease in locomotor activity, rather a biphasic increase was observed. The effects of 8-OH-DPAT on locomotor activity immediately post-injection are interpreted as being a result of the stereotyped, uncoordinated "ambulation" which forms a part of the 5-HT syndrome, and which results in a level of activity intermediate between that of unhabituated and habituated rats.(ABSTRACT TRUNCATED AT 250 WORDS)