Tanford [Tanford, C. (1979) Proc. Natl. Acad. Sci. USA 76, 3318-3319] used thermodynamic arguments to show that the pressure difference across the bilayer of small phospholipid vesicles must be zero. This paper analyzes the implications of this conclusion in terms of Laplace's law and the basic thermodynamics of interfaces. In its usual form, Laplace's law is of questionable value for the vesicle. If the vesicle is in a state of metastable equilibrium, the surface free energy must be minimal with respect to several thermodynamic variables; the condition (delta F/ delta A) = 0 is not adequate by itself.