Although lipid structure in models for the stratum corneum (SC), the main barrier to skin permeability, has been extensively studied, only limited data are extant concerning the kinetic mechanism for the formation of domains, lamellar phases, and lipid packing motifs. Such information would be of substantial interest in the characterization of the effects of disease states which disrupt the barrier. Kinetic IR spectroscopy measurements probed the temporal sequence of molecular events producing ordered structures in a three-component SC model of equimolar ceramide[NS] (cer[NS]), perdeuterated stearic acid-d(35) (SA-d(35)), and cholesterol. Samples, heated above T-m, were quenched to 31 degrees C, and then spectra were recorded at similar to 15 min intervals for a total of 20-150 h. ER provides unique molecular structure information about headgroup H-bonding, lipid packing, and lipid chain order. The following sequence for phase separation was observed: (1) Formation of ceramide amide H-bonds from disordered forms to ordered structures (0.5-4 h); (2) appearance of ordered ceramide chains with some orthorhombically packed structures (0.5-8 h); and (3) phase separation of large orthorhombic domains of SA-d(35) (4-10 h). A spinodal decomposition mechanism, defined by continuous composition changes during the phase separation, suggests a qualitative description for these events.