Women who have palpable breast cysts with intracystic Na/K > 3 may have a lower risk of developing breast cancer than those with intracystic Na/K < 3. In this study significantly higher concentrations of insulin-like growth factor-binding protein-3 (IGFBP-3), insulin-like growth factors I and II (IGF-I, IGF-II) and transforming growth factor-beta 2 (TGF-beta2) were found in the Na/K > 3 sub-group. No difference was found in transforming-growth factor-beta 1 (TGF-beta1) levels between the two sub-groups of breast cysts. A positive correlation was obtained for IGFBP-3 and TGF-beta1 in the Na/ K > 3 sub-group consistent with reports that TGF-beta1 may regulate the production of IGFBP-3. Equimolar amounts of total IGFs and IGFBP-3 in breast cyst fluid imply that most, if not all, of these IGFs are protein-bound. The significantly higher concentrations of TGF-beta2 in the Na/K > 3 sub-group may partly explain the lower risk of breast cancer in this group of women.