In order to induce the primary antibody response to sheep erythrocytes in vitro in murine lymphocytes, the cells are usually cultured in RPMI-1640 medium containing 10% fetal calf serum (FCS). When FCS was replaced by calf serum (CS) or newborn bovine serum (NBS), the antibody response was poor compared with that obtained with FCS. However, a comparable response was induced when CS or NBS was added at 1% to the culture medium in combination with 500 micrograms/ml beta-cyclodextrin (beta-CD). In the presence of beta-CD, the response was the highest when CS or NBS was added at 1%. An important observation was that all the lots of CS (5 lots) and NBS (2 lots) tested supported the response equally in the presence of beta-CD. The anti-sheep erythrocytes response induced by 1% CS or NBS in the presence of beta-CD was shown to be completely dependent on the added antigen, suggesting that beta-CD is not a polyclonal activator. beta-CD showed neither mitogenic nor cytotoxic effects on murine lymphocytes. These results indicate that beta-CD is a useful additive for inducing the primary antibody response in vitro in the culture medium containing CS or NBS which is usually less supportive but less expensive than FCS.