Antisera used in immunological assay systems for small molecular weight substances are routinely prepared by coupling the hapten to a carrier protein via a chemical linker. Often this bridge is partly recognized by the antibody, resulting in reduced sensitivity when an identically structured tracer (e.g. iodine-labelled) is used. Historically, the problem was solved by changing the linking structures in the tracer. An alternative way is exemplified by the development of a very sensitive and specific iodinated radioimmunoassay for melatonin. This new approach involves the design of a linkage identical in the tracer and the antigen that is both very short and closely resembling the structure of the analyte itself.