The phagocytic activity of peripheral blood monocytes from sickle cell disease patients and normal controls was studied using a monocyte monolayer assay. Phagocytosis of antibody-coated red cells by monocytes from patients in stable condition and in normal controls did not differ significantly (7.1 ± 1.5 vs. 5.3 ± 0.9%). However, monocytes from sickle cell disease patients during vasoocclusive crises demonstrated increased phagocytic activity compared to the normal controls (11.0 ± 2.7 vs. 5.3 ± 0.9%, p < 0.025). Numerous defects in immune response have been described in association with sickle cell disease. However, monocyte phagocytic activity is not deficient and is not a factor in the predisposition to infections.