An NMR method is presented for measuring compartmentspecific water diffusion coefficient (D) values. It uses relaxography, employing an extracellular contrast reagent (CR) to distinguish intracellular (IC) and extracellular (EC) 1 H 2 O signals by differences in their respective longitudinal (T 1 ) relaxation times. A diffusionweighted inversion-recovery spin-echo (DW-IRSE) pulse sequence was used to acquire IR data sets with systematically and independently varying inversion time (TI) and diffusion-attenuation gradient amplitude (g) values. Implementation of the DW-IRSE technique was demonstrated and validated using yeast cells suspended in 3 mM Gd-DTPA 2-with a wet/dry mass ratio of 3.25 : 1.0. Twodimensional (2D) NMR data were acquired at 2.0 T and analyzed using numerical inverse Laplace transformation (2D-and sequential 1D-ILT) and sequential exponential fitting to yield T 1 and water D values. All three methods gave substantial agreement. Exponential fitting, deemed the most accurate and time efficient, yielded T 1 : D (relative contribution) values of 304 ms : 0.023 ร 10 -5 cm 2 /s (47%) and 65 ms : 1.24 ร 10 -5 cm 2 /s (53%) for the IC and EC components, respectively. The compartment-specific D values derived from direct biexponential fitting of diffusion-attenuation data were also in good agreement. Extension of the DW-IRSE method to in vivo models should provide valuable insights into compartment-specific water D changes in response to injury or disease.