The temperature and hydration dependences of lipid lateral diffusion in model membrane-D2O multilayers of dipalmitoyl (DPL), dimyristoyl (DML), dilauryl (DLL), and egg yolk (EYPC) lecithins were measured by using pulsed gradient proton NMR spin-echo techniques. Oriented samples were used to minimize anisotropic dipolar interactions and permit formation of a spin-echo. A general discussion of the technique and of the possible errors is included. Significantly lipid lateral diffusion is hydration dependent over the range studied (15-40% D2O, w/w), varying in DPL over this range, for example, by a factor of 2. For the saturated lipids at the same hydration and temperature, diffusion decreases monotonically as the chain length increases. At a constant hydration of 20% D2O (w/w), the activation energies (kcal/mol) are as follows: EYPC, 9.0 ± 0.4; DLL, 9.4 ± 0.2; DPL, 18.6 ± 1.3; DML, 15.2 ± 0.3. The results tend to be larger, by factors of 2-5, than the earlier ESR spin-label results, the differences being attributable in part to the differences in hydration and to the absence of probe effects in this work. The value of 5 x 10-8 cm2/s for DPL (40% D2O) at 42 °C is slightly larger than the usually reported spin-label value of 2 x 10-8 and than the fluorescence photobleaching recovery measurements which give typically 1 x 10-8 cm2/s. The results agree with recent photo-spin-label measurements. Cholesterol in small amounts (less than 10 mol %) in DPL increases lipid diffusion; its presence in larger concentrations decreases diffusion. © 1979, American Chemical Society. All rights reserved.