Using the technique of somatic cell fusion, a monoclonal antibody to human TSH (hTSH) has been produced. The monoclonal antibody (anti-hTSH 1/1) has an affinity (Kd = 4.04 x 10(-9) M/liter) for hTSH which is slightly less than that of the polyclonal antisera (Kd = 9.8 x 10(-10) M/liter) derived from the same mouse used for the fusion experiment. The beta-subunit of hTSH displays nearly complete cross-reaction, but has a lower affinity (Kd = 2.6 x 10(-8) M/liter) for the monoclonal antibody. hCG and its alpha- and beta-subunits as well as human LH do not cross-react with this antibody. The high specificity of this antibody will make it useful as an immunofluorescent probe of hTSH-secreting cells as well as in the immunoabsorption and purification of hTSH.