The pharmacokinetics of sulfadoxine (SULF) and pyrimethamine (PYR) were studied in 7 healthy volunteers after a single oral dose of Fansidar®. A comparison was made between the pharmacokinetics of the components of Fansidar calculated from whole blood and plasma data. The mean whole blood to plasma concentration ratios of SULF and PYR were 0.62 and 0.87, respectively. The elimination half-lives of SULF and PYR were similar in whole blood and plasma. The apparent volume of distribution and clearance of SULF and PYR in whole blood were significantly higher (p < 0.01) than the corresponding plasma values. Because malaria-infected erythrocytes appear to concentrate SULF, it may be more relevant to measure drug concentrations in whole blood rather than in plasma in assessing the antimalarial efficacy of Fansidar.