Cardiotrophin-1 (CT-1) originally was discovered as a factor that can induce hypertrophy of cardiac myocytes, both in vitro and in vivo. Subsequently, CT-1 has been shown to have a wide variety of different effects on cardiac and noncardiac, cells including the ability to stimulate the survival of both cardiac and neuronal cells. Like other members of the interleukin-6 family of cytokines, CT-1 stimulates both the p42/p44 mitogen-activated protein kinase pathway and the Janus activated kinase/signal transducers and activators of transcription pathway. Interestingly, whilst activation of the p42/p44 mitogen-activated protein kinase pathway is necessary for the survival-promoting effects of CT-1 in cardiac cells, it is not required for its hypertrophic effect, which is likely to involve activation of the Janus-activated kinase/signal transducer and activator of transcription-3 pathway. CT-1, therefore, may be of use as a novel cardioprotective agent, particularly if its hypertrophic effect can be specifically inhibited. (C) 1999 Elsevier Science Inc. All rights reserved.