The range of messenger action of a point source of Ca²⁺ or inositol 1,4,5-trisphosphate (IP₃) was determined from measurements of their diffusion coefficients in a cytosolic extract from Xenopus laevis oocytes. The diffusion coefficient (D) of [³H]IP₃ injected into an extract was 283 μm²/s. D for Ca²⁺ increased from 13 to 65 μm²/s when the free calcium concentration was raised from about 90 nM to 1 μm. The slow diffusion of Ca²⁺ in the physiologic concentration range results from its binding to slowly mobile or immobile buffers. The calculated effective ranges of free Ca²⁺ before it is buffered, buffered Ca²⁺, and IP₃ determined from their diffusion coefficients and lifetimes were 0.1 μm, 5 μm, and 24 μm, respectively. Thus, for a transient point source of messenger in cells smaller than 20 μm, IP₃ is a global messenger, whereas Ca²⁺ acts in restricted domains.