Peripheral blood lymphocytes from 24 patients with well-defined immunodeficiency were studied for membrane characteristics and in vitro responsiveness to various stimuli. The mean percentages of lymphocytes bearing easily detectable surface immunoglobulin (Ig) were similar to those of normals except in patients with infantile x-linked agammaglobulinemia (X Ag) who had a significantly lower percentage of only 1.9% Ig bearing cells (p < 0.001). Despite their marked deficiency in surface Ig bearing cells, patients with X Ag had normal percentages of complement receptor rosettes (EAC, HEAC, or B cell rosettes); percentages of these cells were also normal or elevated in the other patient groups. Percentages of spontaneous sheep erythrocyte rosettes (E or T cell rosettes) were significantly increased in X Ag patients and reduced in patients with ataxia telangiectasia and isolated IgA deficiency. Lymphocyte 3H-thymidine incorporation in response to each of the three mitogens, phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM), was usually normal except in X Ag patients where, in several evaluations, the responses of peripheral blood lymphocytes to PHA were significantly lower than those of normal control cells (p < 0.001). Responses to Con A and PWM were normal or elevated in those same experiments. The selective hyporesponsiveness of X Ag lymphocytes to PHA suggests that these patients may be deficient in a restricted population of T cells. It is possible that this population may be necessary for the full maturation of B cell function. Lymphocytes from all patients, including agammaglobulinemic patients, responded normally to stimulation with one or more antigens.