The circulating concentration of endometrial protein PP14 varied during the menstrual cycle in patients with endometriosis. The highest levels were found on days 1 to 4 of the cycle (176 +/- 123 micrograms/L; mean +/- SD), and the lowest on days 5 to 20 (44.1 +/- 29.7 micrograms/L). Rising levels were observed on days 21 to 30 (58.3 +/- 62.6 micrograms/L). On days 5 to 20 (i.e., during period of the lowest levels) patients with advanced endometriosis had higher PP14 levels (63.9 +/- 39.0 micrograms/L) than those with mild endometriosis (29.3 +/- 18.2 micrograms/L; p less than 0.01). Patients with mild endometriosis had slightly higher serum PP14 levels than apparently healthy control subjects (p less than 0.05), but overlapping of values between the two groups is remarkable. Conservative surgical elimination of endometriosis significantly decreased the serum PP14 levels. Treatment with danazol (600 mg/day), or with medroxyprogesterone acetate (100 mg/day) after laparoscopy also resulted in significant decreases in the serum PP14 concentration. After 6 months of treatment, conservative surgery in combination with danazol or with medroxyprogesterone acetate, yielded more pronounced declines in serum PP14 level than conservative surgery plus placebo. No significant difference was observed between the effects of danazol and medroxyprogesterone acetate. We conclude that endometriosis tissue contributes to the circulating PP14 level, and the decline in PP14 level during danazol and medroxyprogesterone acetate treatments reflects regression of intrauterine and ectopic endometrial tissues.