Vangueria infausta burch subsp. infausta (Rubiaceae) produces fruits eaten by humans and animals. The leaf, fruit, stem bark and root bark are used as a remedy for many ailments and the roots are used to treat malaria. In this study, concentrations of fractions of the V. infausta root bark extract that produce 50% inhibition (IC50) are determined using the ability of the extract to inhibit the uptake of [G3H]-hypoxanthine by P. falciparum cultured in vitro. The root bark extract showed antimalarial activity against Plasmodium berghei in mice. It gave a parasite suppression of 73.5% in early infection and a repository effect of 88.7%. One fraction obtained from a chloroform extract gave an IC50 value of 3.8 +/- 1.5 microg/mL and 4.5 +/- 2.3 microg/mL against D6 and W2 strains of P. falciparum, respectively, and another from the butanol extract gave an IC50 value of 3.9 +/- 0.3 microg/mL against the D6 strain. Chloroquine had an IC50 value of 0.016 microg/mL and 0.029 microg/mL against D6 and W2 strains, respectively. The plant showed the presence of flavonoids, coumarins, tannins, terpenoids, anthraquinones and saponins.Vangueria infausta burch subsp. infausta (Rubiaceae) produces fruits eaten by humans and animals. The leaf, fruit, stem bark and root bark are used as a remedy for many ailments and the roots are used to treat malaria. In this study, concentrations of fractions of the V. infausta root bark extract that produce 50% inhibition (IC50) are determined using the ability of the extract to inhibit the uptake of [G3H]-hypoxanthine by P. falciparum cultured in vitro. The root bark extract showed antimalarial activity against Plasmodium berghei in mice. It gave a parasite suppression of 73.5% in early infection and a repository effect of 88.7%. One fraction obtained from a chloroform extract gave an IC50 value of 3.8 +/- 1.5 microg/mL and 4.5 +/- 2.3 microg/mL against D6 and W2 strains of P. falciparum, respectively, and another from the butanol extract gave an IC50 value of 3.9 +/- 0.3 microg/mL against the D6 strain. Chloroquine had an IC50 value of 0.016 microg/mL and 0.029 microg/mL against D6 and W2 strains, respectively. The plant showed the presence of flavonoids, coumarins, tannins, terpenoids, anthraquinones and saponins.