The majority of naturally occurring biological and chemical toxins are highly lethal, nonproteinaceous, low molecular weight substances which exert their toxicity through a variety of mechanisms. Their relative small size and extreme in vivo toxicity have hampered the development of protective vaccines. We have investigated the feasibility of anti-idiotype-based vaccines which utilize antibodies for inducing a systemic and protective immunity against the in vivo toxicity of some of these toxic substances. A murine IgG1 monoclonal anti-T-2 mycotoxin antibody protective against mycotoxin toxicity was generated. This antibody was used to produce a second generation monoclonal anti-idiotype antibody which was capable of serologically mimicking the tertiary conformation of the nominal antigen, i.e., T-2 mycotoxin. Administration of the monoclonal anti-idiotype antibody to mice induced a circulating and protective antibody response against the in vitro and in vivo toxicity of T-2 mycotoxin. Antibody-based vaccines may represent the only safe and effective strategy for the design of protective vaccines against small nonproteinaceous toxic compounds whose extreme toxicity prevents their use as safe immunogens. The potential of antibody-based vaccines for producing protective immunity against low molecular weight chemical and biological toxins is discussed.