The in vitro distribution of the antimalarial drug halofantrine was measured in drug-preincubated whole blood after separation of the blood cells from the plasma according to their type. In normal blood, halofantrine was mainly associated with plasma (85% of the total drug) and to a lesser degree with erythrocytes (11%). The drug accumulated in lymphocytes to an approximately 250-fold higher concentration than in normal erythrocytes, but this represented only a small fraction (1%) of the total drug. It was not significantly bound to thrombocytes (2%), lymphocytes (1%) or granulocytes (0.3%). The distribution of halofantrine into Plasmodium falciparum-parasitised red blood cells was measured at different parasite stages and with varying serum concentrations. Halofantrine accumulated in P. falciparum-parasitised red blood cells to concentrations up to 60-fold those found in normal erythrocytes. The amount of accumulated drug depended on the parasite stage and presence of serum, since mature parasites showed the highest accumulation, and serum reduced drug accumulation compared to incubation under standard cultivation conditions.