OBJECTIVE The aim of this work was to investigate peroxidase activity in human tears during the various phases of the menstrual cycle. For comparative purposes saliva was also examined. METHODS Tear fluids and saliva from 10 healthy volunteers 23-41 years of age (mean: 28.2 years), with regular menstrual cycles were sampled for the duration of at least two complete cycles. Menstrual cycles and ovulation periods were evaluated by measuring morning body temperature and hormone levels in plasma and urine. Unstimulated tears and unstimulated saliva were collected in the morning every two days. Peroxidase activity was monitored according to the 5,5'-dithiobis, 2-nitrobenzoic acid thiocyanate (Nbs-SCN) method and the protein content was determined by the Bradford method. RESULTS Peroxidase activity in tears, expressed as U/mL, was significantly (p <.05) higher during the preovulatory and luteal phases with respect to the menses, whilst total protein content remained almost unchanged throughout all phases. A positive correlation was found between lacrimal fluid peroxidase activity and 17beta-estradiol plasma levels (p <.001). Salivary peroxidase activity did not show such estrogen-related changes. CONCLUSIONS Our findings report cyclic variations in peroxidase activity in human tears during the menstrual cycle. Such cycling seems to reflect variations of 17 beta-estradiol plasma levels. These results suggest that a regulation of lacrimal fluid peroxidase by 17 beta-estradiol could be one possible cause for the female gender predilection in some ocular diseases, such as keratoconjunctivitis sicca.