Proenkephalin peptide F [107-140] is an enkephalin-containing peptide found predominantly within the adrenal medulla and is co-packaged with epinephrine within adrenal medullary chromaffin granules. Peptide F has been shown to have the classic opioid analgesia effects along with immune cell interactions. This is only the second peptide F study in women, and in it we compare the responses of peptide F to a maximal cycle exercise test and recovery values over the follicular and luteal phases of the menstrual cycle. Eight untrained (directly documented in this study) women who were eumenorrheic performed a progressive maximal exercise test to volitional exhaustion on a cycle ergometer, once during the follicular phase, and once during the luteal phases of the menstrual cycle. Blood was obtained pre-exercise, immediately post-exercise and at 0, 15, and 30 min into recovery. Typical exercise changes in response to the cycle tests were observed with blood lactate increases that remained elevated 30 min into recovery. No significant exercise-induced elevations were observed for peptide F concentrations with exercise nor were any differences observed between the two menstrual phases. Thus, the effects of the menstrual cycle on peptide F concentrations appear to be minimal under the conditions of this investigation. With high concentrations of peptide F observed at rest (approx. 0.2-0.3 pmol ml(-1)) pre-exercise arousal mechanisms may have obviated any exercise-induced response. In addition, inhibition via elevated epinephrine may have inhibited any post-exercise increases and finally adrenal medullary capacity for circulatory concentrations of peptide F may have been reached in such untrained women. Pre-exercise arousal mechanisms potentially related to analgesia may also be involved to prepare untrained women for the stress of maximal exercise.