A relationship between zinc deficiency and lymphocyte function in children with sickle cell disease (SCD) has been suggested. Number and function of B and T lymphocytes were assessed in 3 matched groups of children: normal subjects with Hb A and normal zinc; patients with SCD; and normal zinc (SCD-N); and patients with SCD and decreased zinc (SCD-D). Percentages of B and T cells, response to cutaneous antigens and increases in tetanus antibody titres were similar among all groups. Absolute numbers of WBC, lymphocytes and B and T cells were markedly increased in SCD-N (p less than 0.001) and to a lesser degree in SCD-D (p less than 0.01). Controls and SCD-N had a normal response to all mitogens, which was not inhibited by SCD-D sera. SCD-D had a depressed response to PHA (p less than 0.001), which was not corrected by zinc addition in vitro. These findings indicate that B cell function and T cell-dependent delayed hypersensitivity are normal in children with SCD and are independent of body zinc status. They also suggest some abnormality of T helper cells in the presence of zinc deficiency, and in the absence of a demonstrable serum inhibitor.