Young patients with Down's syndrome (DS) have high rates of infections, malignancies and autoimmune phenomena. Therefore, DS may be considered as a model of precocious, abnormal ageing of the thymus-dependent system in man. In DS children less than 6 years of age, the levels of serum immunoglobulins did not differ from healthy controls, but after that age, considerable hyper-IgG and -IgA were found. Furthermore, high levels of IgG1 and IgG3 have been found, whereas a progressive decline of IgG2 and IgG4 with age has been observed. The frequency of hepatitis B virus carriers even in the youngest age group is much higher among DS children. It has been reported that an IgG response was detectable in 75% of controls after HBsAg vaccination as compared to the 16.6% of DS patients. The presence of autoantibodies against human thyroglobulin did show a positive association with HB Virus Ag carriers, but only in the oldest DS subjects. Natural antibodies against intestinal antigens are low, while in the presence of cow's milk, abnormally high titres against casein and beta-lactoglobulin were present. High levels of IgG antibodies against gliadin have been observed. In spite of a normal percentage of CD3- and CD2-positive lymphocytes, a high proportion of cells express low-avidity receptors for sheep erythrocytes. Although the proportion of CD4+ T-lymphocyte helper-cells is normal, a marked imbalance in the CD4+ subpopulations has been documented. The percentage of suppressor-cytotoxic CD8+ lymphocytes is markedly increased. The responses to phytohemagglutinin and concanavalin A are within the normal range in the first decade of life and decline progressively thereafter. A recent study reported defective proliferative response to allo-mixed lymphocyte culture, with decreased expression of the membrane CD25, low secretion of interleukin 2 in the supernatant and depressed allo-specific cytotoxic activity.(ABSTRACT TRUNCATED AT 250 WORDS)