This investigation was designed to determine how information about the lipid chain melting and structural characteristics of sn-1 saturated/sn-2 monounsaturated phosphatidylethanolamines, a subclass of naturally occurring phospholipids, can be generalized among these lipid molecules. Specifically, 30 molecular species of sn-1 saturated/sn-2 unsaturated monoenoic phosphatidylethanolamines were semi-synthesized. The phase transition behavior of these monoenoic lipids in excess water was studied calorimetrically. The computer-based molecular mechanics approach was used to simulate the energy-minimized structures and to calculate steric energies for the diglyceride moieties of some of the 30 monoenoic lipid molecules, at T < Tm, in various aggregated states. These combined calorimetric and computational studies led to the following results and conclusions. 1) For a homologous series of monoenoic lipids with a common molecular weight and with a cis-double bond at various positions along the sn-2 acyl chain, the characteristic reduction of the main phase transition temperature (Tm) is proposed to be a result of an entropy-driven phenomenon. 2) The maximal decrease in the Tm for bilayers prepared from four series of monoenoic phosphatidylethanolamines containing a sn-2 octadecenoyl chain is shown by interpolation of calorimetric data to occur uniquely when the cis double bond is located commonly between C(10) and C(11) positions from the carboxyl end. 3) Monoenoic phosphatidylethanolamines can be divided into two groups. The Tm values obtained with bilayers of monoenoic lipids within each group can be systematically correlated with their structural parameters, leading to the derivation of two general Tm-structure relationships.