The isotopic substitution of deuterium for hydrogen has been shown to markedly alter the relative rates of chemical reactions and to affect the conformation and stability of macromolecules ( 1 ) . The profound physiological and biological changes associated with high degrees of deuteration have been found not to be compatible with survival in the mammalian organism( 2). However, the continuous ingestion with 30% deuterium oxide (DzO, heavy water) appears to have no appreciable effects on the body weights, general well-being or life span of the laboratory mouse(3). We have recently demonstrated the protective effects of this, and lower levels of D 2 0 on mice infected with the Rauscher leukemogenic virus (4). The mechanism of protection appeared to be depression of the neoplastic proliferation of lymphoreticular cells. In view of similarities noted between cells undergoing leukemic proliferation and those responding immunologically ( 5) it seemed feasible to investigate the effects of deuteration on the immune response.Matwials and methods. Deuterium oxide (supplied as 99.7% DzO by the Richland Operations Office of the U. S. Atomic Energy Commission, Richland, Wash.) was purified by distillation from alkaline permanganate. BALB/c/jax female mice, 5-7 weeks old, were fed a standard pellet diet and deuterium was administered as drinking water ad libitum at a concentration (v/v) of 30% for the duration of the experiments.Mice received a single intraperitoneal injection of 1.25 mg bovine serum albumin (BSA, crystalline, Pentex, Inc., Kankakee, Ill.) in 0.25 ml of a complete Freund's adjuvant emulsion (Difco Laboratories, Detroit) either 10 days or 17 days after they started drinking heavy water. Sheep erythrocytes were washed 3 times in 20 volumes of cold saline and the packed cells suspended in *Sumpported by U. S. Atomic Energy Commission Contract RLO-192 '1-3. 2 volumes of saline for intraperitoneal injection either as a single dose of 0.25 ml or as two 0.25 ml inoculations 18 hours apart. Mice were bled periodically from the retro-orbital plexus. Antibody titers to BSA were determined by the agglutination of tanned, antigencoated sheep erythrocytes as described by Stavitsky (6). Red cell agglutinins were determined directly in a 2-fold serial dilution system in the presence of 1:200 saline diluted normal rabbit serum. To assay macroglobulin agglutinin activity, aliquots of mouse antisera were incubated for 18 hours at 25°C in phosphate buffered saline, pH 7.4, containing 0.1 M 2-mercaptoethanol(7). Serial dilutions and assays were carried out directly in this medium. Statistical significance of data was determined by student t-test analysis of reciprocal logarithmic (base 2) titer values. Both BSA-adjuvant and sheep erythrocyte immunization experiments were repeated twice using 5-8 mice in each group with similar results as reported below.Results. The antibody response of mice drinking 30% D20 is illustrated in Fig. 1. Mice drinking heavy water continuously starting 10 days in advance of immunization showed no sig...