Abstract: Cardiotrophin-1 (CT-1) was cloned from mouse embryoid body for its ability to induce growth of heart cells. Predictions of its secondary structure indicate that CT-1 belongs to a family of cytokines with a four-helical bundle structure, and sequence comparisons reveal a weak homology to leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF). Using a reverse transcriptase-polymerase chain reaction assay with rat sympathetic neuron cultures, we find that CT-1 induces and suppresses the expression of the same set of neuropeptide and neurotransmitter synthetic enzyme mRNAs as do LIF and CNTF. In addition, the effects of CT-1 and LIF are not additive, and CT-1 does not require a GPI-linked component to mediate its actions. Our functional data confirm that CT-1 is a member of the neuropoietic cytokine family and suggest that the CT-1 receptor complex contains the gp130 signal transducing component.