Heparin inhibits essential erythrocyte invasion events. (A) Heparin effectively inhibited merozoite invasion of P falciparum lines W2mef (sialic acid–dependent invasion phenotype) and 3D7 (sialic acid–independent invasion phenotype) at comparable levels. CSC was noninhibitory against all lines tested; data are excluded from panels B through D for clarity. (B) Heparin had similar inhibitory activity against invasion of 3D7 P falciparum into neuraminidase-, chymotrypsin-, or trypsin-treated erythrocytes versus untreated erythrocytes. (C) Heparin efficiently inhibited invasion of W2mef P falciparum into chymotrypsin- and trypsin-treated erythrocytes compared with untreated. (D) 3D7 parasites were selected once or twice for invasion of erythrocytes in the presence of heparin 100 μg/mL. The ability of heparin to inhibit erythrocyte invasion by merozoites was comparable between the parent parasites and heparin-selected parasites. All data are mean growth ± SEM, expressed as percentage of control (PBS; 3 assays in duplicate), except for panel B mean ± growth range, expressed as percentage of control (PBS; 2 assays in duplicate).