The pituitary gland appears to be a new source for novel immunoregulatory peptides and proteins. In this chapter, we have detailed a method of assay and purification to homogeneity for one such protein, SPN. When using an activity as a means of purification, it is essential to rapidly establish that the substance is not a previously identified molecule. To this end, we have developed a monospecific polyclonal antibody to SPN and used this to screen a pituitary cDNA library. The sequence of the positive clone then clearly establishes the uniqueness of the factor. In a general sense, these findings introduce the concept of identification of new immunoregulatory substances in the neuroendocrine system and hormones in the immune system. In a specific sense, they have resulted in the discovery of a new and important immunoregulatory protein. © 1991 ACADEMIC PRESS, INC.