The control of porosity morphology and physico-chemical characteristics of calcium phosphate bone substitutes is a key-point to guaranty healing success. In this work, micro- and macroporosity of materials processed with 70% Hydroxyapatite (HAP) and 30% beta-tricalcium phosphate (beta-TCP) were controlled by sintering temperature and porogen addition, respectively. Porosity was quantified by scanning electron microscopy (pore size) and mercury intrusion porosimetry (interconnection between pores). The content of macrointerconnections and their size were dependent on porogen content, shape, and size. Mechanical properties (compressive strength) were strongly dependent on macroporosity size and content, on the basis of exponential laws, whereas microporosity ratio was less influent. Relying on those results, three types of materials with contrasting porous morphologies were processed and assessed in vitro, in primary culture of human osteoblasts and fibroblasts. With both types of cells, an exponential cellular growth was effective. Cells colonized the surface of the materials, bridging macroporosity, before colonizing the depth of the materials. Cell migration across and into macroporosity occurred via the emission by the cells of long cytoplasmic extensions that hanged on microporosity. Both macroporosity and macrointerconnectivity size influenced the penetration of cells. An interconnection size of 15 microm appeared to be effective to support this invasion without bringing down mechanical strength.