The ability of Plasmodium falciparum to accumulate 3H-clindamycin, 3H-tetracycline, and 3H-dihydrostreptomycin was determined in synchronized trophozoites and schizonts in 87% parasitemia 5% hematocrit cultures. Accumulation was time-dependent and modestly concentration-dependent. At 0.1 mM initial external drug concentration, the ratio of drug concentration in cells:medium after 120 min was 5.5 for 3H-clindamycin, 2.8 for 3H-tetracycline, and 0.95 for 3H-dihydrostreptomycin. Corresponding values for uninfected erythrocytes were 3.2, 2.3, and 0.78, respectively. These data may explain the lack of antimalarial activity of the aminoglycosides and may partially explain the slow onset of therapeutic action of clindamycin and tetracycline. The low intracellular concentrations attained for the latter two drugs have important implications for understanding the kinetics and mechanism of their antiplasmodial effects.