The anxiolytic and sedative effects of Tilia americana L. var. mexicana (Schltdl.) Hardin inflorescence extracts and its acute toxicity were tested. Sodium pentobarbital (SP)-induced hypnosis potentiation (SPP), as well as ambulatory activity and anti-anxiety response in three different experimental models were evaluated with hexane and methanol extracts in mice. In order to determine the proper timing of assessments and to identify the most active extract, a 100mg/kg dosage of hexane, ethyl acetate and methanol crude extracts were tested on SPP after 15, 30 and 60min of the administration. Then a dose-response curve was made for the hexane (10-1000mg/kg) and methanol (10-300mg/kg) extracts in all experimental models. Both extracts produced a significant and dose-dependent lengthening in the time of SP, with the methanol extract being more potent than the hexane extract at 60min after administration. Moreover, a significant and dose-dependent attenuation in the anxiety-response in the plus-maze test and exploratory cylinder activity, but also a diminution in the ambulatory activity and in the head dipping response were observed resembling the response to diazepam. Acute toxicity was observed with less dose of methanol extract (LD(50)=375mg/kg) in comparison to the hexane extract (LD(50)>2900mg/kg). Results of the present study shows that Tilia americana var. mexicana possesses depressant activity on the CNS similar to the better-studied species of European Tilia and reinforces its use as anxiolytic and sedative in traditional medicine.