Recently, human urocortin II (hUcn II), a member of the corticotropin-releasing factor (CRF) peptide family, was identified. The following experiments sought to compare the effects of this novel CRF-related peptide versus those of ovine CRF (oCRF) on locomotor activation and anxiety-related behavior, using the locomotor activity test and the elevated plus maze, respectively. To examine locomotor activity during the active (dark) and inactive (light) phases, rats were intracerebroventricularly (i.c.v.) injected with 0, 0.1, 1.0 or 10 microg of hUcn II (n=8/group active; n=6-9/group inactive) or oCRF (n=8/group active; n=8/group inactive) 2 h after the onset of their respective testing phase and monitored for 3 (inactive) or 5 (active) h. To compare the effects of CRF-related peptides on exploration of the elevated plus maze, rats were pretreated (i.c.v. 0, 0.1, 1.0 or 10 microg) with hUcn II (n=7-11/group) or oCRF (n=7-10/group), 10 min prior to testing. Delayed effects in the elevated plus maze were examined in rats injected with 1.0 microg of hUcn II (n=8/group) or oCRF (n=6-8/group), or vehicle (n=8/group) 1, 4 or 6 h before testing. In contrast to the activational effects of oCRF, hUcn II mildly suppressed locomotor activity during the inactive phase. hUcn II did not acutely affect open arm exploration in the elevated plus maze, whereas oCRF decreased this measure. However, hUcn II increased open arm exploration 4 h after injection. Thus, hUcn II exhibits mild motor suppressive effects and delayed anxiolytic-like effects, suggesting a time-dependent role for hUcn II in the regulation of stress-related behavior.