The production of antibodies against human choriogonadotropin (hCG) was studied in normal and athymic (nu/nu) mice of two strains (C57/BL and Balb/c), injected with native (whole) hCG or an immunogen consisting of a synthetic hCG beta COOH-terminal peptide, residues 109-145, conjugated to diphtheria toxoid and mixed with a synthetic muramyl dipeptide analog (nor-MDP) as adjuvant. Both the short-term effect of native hCG dissolved in saline and injected IM (primary response), and the long-term effect of the native hCG and of the hCG immunogen dissolved in saline, emulsified in squalene-Arlacel A, and injected SC as a depot injection (secondary or memory response), were considered. The results obtained indicate that native hCG may be classified as a T-cell independent antigen in the sense that it can elicit low levels of IgM antibodies on a short term basis in athymic mice that have either no or very low T-cell levels. In long-term studies using hCG and the hCG immunogen no antibodies could be detected in athymic mice 14 days after a booster inoculation given 28 days after primary immunization, a regimen that produced high levels of antibodies in normal mice. Because of their inability to sustain humoral responses to native hCG as well as to other hCG immunogens, athymic mice seem well suited for in vivo studies of some of the biological effects of hCG.