Fragments of short ragweed extract were prepared by peptic digestion and fractionated by molecular exclusion chromatography. We focused on fragmenting a ragweed fraction that was enriched for Amb a I. Digestion products in the molecular weight range of 5–15 kD (fSRW) were examined for their antigenic, immunogenic and immunosuppressive properties. fSRW was poorly immunogenic and unable to induce ragweed-specific PCA reactions in rat skin or to bind to anti-ragweed IgG antibodies. Intravenous administration of fSRW either prior to or after intraperitoneal immunization with a ragweed preparation resulted in a significant suppression of the immune response. T cells isolated from lymph nodes of mice immunized with ragweed were stimulated by fSRW in a lymphoproliferation assay. Moreover, T cells from mice injected with fSRW were immunosuppressive when transferred into mice immunized with intact ragweed antigens. Our data demonstrate that peptic fragments (fSRW) of ragweed lack B-cell determinants while retaining their T-cell immunoregulatory properties. Potentially these peptides are less likely to cause adverse reactions in allergen sensitive patients and thus offer a new approach to allergen immunotherapy.