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The present study compared the effects of a wide range of 5-hydroxytryptamine (5-HT)-modulating and potential anxiolytic agents in the rat elevated plus-maze using spatiotemporal (i.e., open arm time and entries) and ethologically derived measures (i.e., risk assessment activities and directed exploration). The drugs used were 5-HT_1A receptor partial (buspirone and ipsapirone) and full (8-OH-DPAT and flesinoxan) agonists, mixed 5-HT_2A/2C receptor antagonists (ritanserin, ketanserin, mianserin, and pirenperone), selective 5-HT₃ receptor antagonists (ICS 205-930, MDL 72222, ondansetron, and (RS)-zacopride), and selective (fluoxetine, fluvoxamine, and zimelidine) and nonselective (imipramine) 5-HT reuptake inhibitors. Only buspirone and mianserin produced effects indicative of an anxiolytic-like action on the spatiotemporal measures. However, all 5-HT_1A receptor ligands, as well as mianserin, ketanserin …