Cholinergic neuronal differentiation factor, CDF, causes a transition from noradrenergic to cholinergic phenotype in cultured sympathetic neurons. Moreover, its identification with leukemia inhibitory factor has shown that CDF is a multifunctional cytokine. To examine the physiological role of CDF and to further elucidate the as yet unknown effects of CDF on the nervous system, two kinds of function-blocking antibodies were generated. One type, raised against whole native CDF, completely blocks CDF activity, whereas the other type, raised against a synthetic peptide corresponding to the N-terminal amino acid region of CDF, blocks activity partially. All three anti-CDF and two antipeptide polyclonal antibodies tested in this study significantly inhibit CDF function.