PURPOSE: Neuregulins (NRG) are growth factors that bind to receptors of the erbB family, and are known to mediate a number of processes involved in diverse tissues. Neuregulin-1beta is expressed in skeletal muscle and is activated by exercise. We hypothesized that NRG-1beta might circulate in the bloodstream and increase as a consequence of physical activity. A study was conducted in healthy subjects to determine if NRG-1beta is immunodetectable in human serum, and if so whether levels relate acutely or chronically to exercise. METHODS: Nine healthy men underwent three bouts of exercise of varying degrees of intensity on a bicycle ergometer over a period of three weeks. Cardio-respiratory fitness was determined by measurement of maximal oxygen uptake (VO(2)max). Serum was sampled prior to and immediately after each session (up to 30 minutes post) and serum NRG-1beta was quantified utilizing an indirect sandwich ELISA assay developed in our lab. RESULTS: Across subjects, mean serum NRG-1beta levels ranged from 32 ng/mL to 473 ng/mL. Individual subjects showed relatively stable levels during the study period that did not change acutely after exercise. Serum NRG-1beta demonstrated a positive correlation with VO(2)max (r2=0.49, p =.044). CONCLUSIONS: These preliminary observations suggest that at least in healthy men, serum NRG-1beta is an indicator of cardio-respiratory fitness and does not change acutely with exercise.