Sympathetic neurons innervating sweat glands undergo a target-directed switch in neurotransmitter properties. Although the factor responsible for inducing this switch has not been identified, it appears to be a member of the neuropoietic cytokine family. Cardiotrophin-1 (CT-1), a new family member, was analyzed to determine whether it was a relevant factor. CT-1 induced choline acetyl-transferase and vasoactive intestinal peptide in cultured sympathetic neurons, and RT/PCR amplified CT-1 mRNA from footpad total RNA. The differentiation activity of CT-1 was blocked by CT-1 antiserum. The activity in sweat gland extracts and cultures was not, however, suggesting that CT-1 is not the sweat gland-derived factor.