This study evaluated the effect of human plasma on the in vitro bactericidal activity of the novel diaminopyrimidine iclaprim against methicillin (meticillin)-susceptible and -resistant Staphylococcus aureus strains. MICs and minimal bactericidal concentrations (MBCs) of iclaprim, with approximately 93% protein binding, were similar in the absence and in the presence of 50% human plasma; MICs and MBCs ranged from 0.06 to 0.125 microg/ml. Furthermore, the activity of iclaprim was not affected by plasma, with > or = 99.9% reduction in CFU after 5.0 to 7.6 h.