Circulating levels of T-cell subsets and NK cells were determined in 78 patients with primary immunodeficiencies, 35 children with recurrent respiratory infections, and healthy age-matched controls. Normal T cell and natural killer (NK) cell values were observed in individuals with immunoglobulin A (IgA) deficiency and X-linked agammaglobulinemia, while reduced OKT4/OKT8 cell ratios and low levels of 5/9+ T helper cells were found in approximately 60% of patients with common variable immunodeficiency. Infants with severe combined immunodeficiency (SCID) and lymphopenia had virtually no cells expressing T-cell or NK-cell surface antigens, but had normal numbers of monocytes and other types of blood cells. Infants with DiGeorge syndrome, other primary T-cell defects, or SCID with B cells had few or no circulating cells of mature T helper-suppressor phenotypes, but had normal numbers of NK cells (HNK-1+) and NK function. These results support the idea of a common stem cell precursor for T, B, and NK cells, each of which follows a separate pathway of differentiation. Profound alterations were observed in the distribution and function of T-cell subsets in ataxia-telangiectasia patients who were previously shown to have thymic dysplasia. A significant reduction in the frequencies of OKT3+ and OKT4+ cells was observed in children with frequent respiratory infections during infancy.(ABSTRACT TRUNCATED AT 250 WORDS)