Chronic lymphocytic leukemia developed in four of five siblings, whose father succumbed to the same disease. The pattern of immune deficiency in the leukemic siblings resembled that found in nonfamilial cases of chronic lymphocytic leukemia, and was correlated with the severity of clinical involvement. In three siblings the peripheral blood leukemic cells shared delta-heavy and kappa-light chains as the only detectable surface immunoglobulin, suggesting that on a cellular and molecular level the chronic lymphocytic leukemia in family members is identical. The fourth and youngest sibling had no peripheral blood lymphocytes with detectable surface immunoglobulin. An inherited defect in the class of cells destined to express delta-heavy and kappa-light chains appears to underlie susceptibility to leukemia in this family.