Docosahexaenoic acid (DHA) and two of its lipoxygenase end-products, the 11- and 14-hydroxy derivatives, of biological relevance were studied for their privileged conformations using molecular mechanics. As an isolated molecule, DHA adopted helical conformations. However, a more extended helical conformation would fit better with the hydrophobic interactions expected with DHA esterified within glycerophospholipids. The most stable conformations of the hydroxy derivatives of DHA appeared as coiled ones where an intramolecular hydrogen bond occurs between the carboxylic and the hydroxy groups. Among the latter conformations, one for each hydroxy derivative would fit better with the requirement of the largest distance between the hydrophobic and hydrophilic centers within the molecule for being inserted in membrane phospholipids where the hydroxy derivatives are likely to be located in their unesterified form. As thromboxane A(2) (TXA(2)) antagonist, DHA and its hydroxy derivatives were compared with minimized conformations of TXA(2) and one of its potent antagonist recently described, (R)-(+)-TCV-144. Interestingly, the 14-hydroxy derivative of DHA, previously reported as the most potent TXA(2) antagonist among the DHA derivatives, exhibited stable conformations quite similar to those of TXA(2) and (R)-(+)-TCV-144.