Abstract: A specific binding assay composition and method for determining a ligand in a sample are disclosed. The composition comprises (a) a binding partner for the ligand; (b) a detection system which has at least two components; (c) a selectively accessible vesicle having a surface-incorporated ligand or ligand analog and a first component of the detection system therein; (d) a substance which modifies vesicle accessibility in response to binding of surface-associated ligand or ligand analog and binding partner; and (e) at least one additional component of the detection system which is reactive with the first component to produce a detectable response which is reduced by association of the binding partner and vesicle modifying substance with the variabily accessible vesicle. A decrease in signal is measured upon reaction as compared to the signal of unreacted vesicles.