The nearest-neighbor recognition method is applied to the problem of phospholipid clustering in bilayers composed of di[1,2-dimyristoyl-sn-glycero-3-phosphoethanol(3'-thio)propionamide] (I), di[1,2-distearoyl-sn-glycero-3-phosphoethanol(3'-thio)propionamide] (II), and 1,2-dimyristoyl-sn-glycero-3-phosphoethanol- (3'-thio)propionamide-1,2-distearoyl-sn-glycero-3-phosphoethanol(3'-thio)propionamide (III). The value and the composition dependency of the apparent equilibrium constant, K, defined by the equilibrium concentrations of homodimers (I and II) and the corresponding heterodimer (III), allow one to distinguish among three fundamentally different classes of clustering: (i) random clustering, (ii) cooperative clustering, and (iii) nonrandom-noncooperative clustering. Experimental results indicate that random clustering of these phospholipids is pervasive in fluid bilayers, whereas cooperative clustering exists in the gel-fluid coexistence region. In the physiologically relevant fluid phase, these same lipids give rise to nonrandom-noncooperative clustering when cholesterol has been included in the bilayer.