Abstract: The aqueous leaf extract of Byrsocarpus coccineus Schum and Thonn. (Connaraceae) was investigated for antipyretic activity in rats and rabbits using yeast, amphetamine and lipopolysaccharide induced pyrexia models. In control rats, yeast (10 mL kg-1, s.c.) caused elevation of rectal temperature of 1.68°C 19 h after administration. The extract (100, 200 and 400 mg kg-1, p.o.) produced a significant (p<0.05) dose dependent inhibition of temperature elevation. Peak inhibitory effect was observed at 1 h post therapy (42.05, 47.16 and 63.64% inhibition, respectively for the extract at 100, 200 and 400 mg kg-1). The effect at 400 mg kg-1 was greater than that of acetylsalicylic acid, ASA (100 mg kg-1, p.o.; 43.18%). An elevation in rectal temperature of 1.88°C was provoked in control rats by amphetamine (10 mg kg-1, i.p.) 0.5 h after administration while in control rabbits, lipopolysaccharide from E. coli (0.2 μg kg-1, i.v.) elicited an elevation of 1.11°C, 1.5 h post challenge. In both models, the extract produced a significant (p<0.05) dose and time dependent direct reduction of elevated temperature with peak effect observed at 3.5 h post therapy. Percent reduction of fever values were 50.24, 61.11 and 84.33, respectively for the extract at 100, 200 and 400 mg kg-1 (p.o.) in respect of the amphetamine test. The effect at 400 mg kg-1 was about the same as that of ASA (85.31%) in this case, but it was lower (44.90%) compared to the standard drug (96.64%) in the lipopolysaccharide test. The results obtained in this study suggest that the extract possess antipyretic activity.