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Aqueous extracts of mouse submaxillary glands yield six peaks on Sephadex G-75 columns, each containing several molecular species. Two of these fractions (III and IV) have a profound effect on the immune response. When given a day before immunization with sheep erythrocytes, the number of antibody-producing cells is reduced ten-fold or more, and the switch from IgM to IgG is virtually absent. Administration two days before or on the day of immunization results in about 50% depression; outside this range there is no effect. The dose-response curve is of sigmoid shape, with the median at about 0.5 mg of fraction III/40 g mouse, reaching an asymptote after doses of greater than or equal to 5 mg at about 5% of the response of untreated mice. Depression of the primary response does not prevent the development of immunological memory: the secondary response is typical in the early and predominant appearance of IgG-producing cells, although their numbers are somewhat lower than in the controls which received no treatment before primary immunization. Treatment on the day before boosting abrogates the secondary response. The immunotranquilizer from mouse submaxillary glands acts equally well on syngeneic and allogeneic recipients, affecting the earliest stage of the immune response. The results are compatible with the induction of a temporary block in the development of helper T cells.