Abstract: To compare the anti-HIV-1 activities of (±)-11-demethyl-calanolide A and its mother compound (±)-calanolide A in vitro and in vivo, the inhibitory activities of the two compounds on HIV-1 reverse transcriptase (RT) were detected in vitro with isotope ³H assay. The cytotoxicity and inhibition of cytopathic effect (CPE )were studied in HIV-1 IIIB infected MT-4 cell cultures by MTT staining method; Mice were given with the two compounds 100 mg·kg^-1 once intraperitoneally, then the mouse sera taken on 30 min and 60 min after administration were detected for the inhibition of HIV-1 RT in vitro. The data showed that (±)-11-demethyl-calanolide A and (±)-calanolide A inhibited HIV-1 RT in vitro with 50% inhibitory concentration (IC₅₀) of (3.028±2.514) μmol·L^-1 and (3.965±5.235) μmol·L^-1, and also inhibited CPE in HIV-1 IIIB infected MT-4 cell cultures with IC₅₀ of (1.081±0.337) μmol·L^-1 and (1.297±0.076) μmol·L^-1, respectively. After intraperitoneal injection of 100 mg·kg^-1 of the two compounds in mice, all the mice sera taken 30 and 60 min afterward inhibited HIV-1 RT in vitro. In comparison with control mice sera, the inhibitory rates of the sera for (±)-11-demethyl-calanolide A were (42.7±1.5)% at 30 min (P<0.01) and (32.2±6.1)% at 60 min (P<0.05), separately, while the inhibitory rates of the sera for (±)-calanolide A were (40.7±6.3)% at 30 min (P<0.01) and (29.2±6.7)% at 60 min. The results suggested that (±)-11-demethyl-calanolide A is a new non-nucleoside HIV-1 RT inhibitor, its anti-HIV-1 activities in vitro, in cell cultures and in mice were slightly higher than that of its mother compound (±)-calanolide A and warrants further studies.