Abstract Zinc deficiency is associated with depression of a number of immune responses. To assess the relationship of zinc and natural killer activity, we studied natural killer activity in adults with sickle cell disease and in two normal volunteers rendered zinc deficient by dietary restriction. Natural killer activity was significantly lower in patients with sickle cell disease and zinc deficiency (5.1 ± 2.9 lytic units per 10 6 cells) than in controls (11.7 ± 5.0 lytic units per 10 6 cells). In the two volunteers, natural killer activity declined during zinc restriction and returned to near initial levels with zinc repletion. These results suggest that zinc deficiency is associated with a lowering of natural killer activity.