Opioid peptides have a variety of pathophysiologic actions, playing a novel important role in human breast cancer. The expression of beta-endorphin was studied in 84 human breast cyst fluids from gross cystic breast disease-affected patients. The concentration of beta-endorphin in pooled breast cyst fluids was over four-fold higher than in respective plasma with a significant increase in the mean value of the 'metabolically active' apocrine cysts when compared with flattened cysts (P < 0.001). The higher levels of Type I cyst suggest de novo mammary synthesis of endogenous opioid peptides and could represent an altered expression of biosynthetic activity of apocrine breast cells, providing a possible explanation on functional changes of gross cysts, on the mechanism of their formation and a perspective relationship to breast cancer risk.