This study describes a detailed investigation of swelling and release behavior of a macromolecule from calcium alginate gel (CAG) beads in the presence of a small molecule, sodium fluorescein (SF). Blue dextran (BD) was used as a model macromolecule. The bead diameter was slightly different after soaking in various concentrations of SF although the SF uptake into calcium gel beads is markedly different. The swelling kinetics of CAG beads showed the rapid hydration and reached a maximum within 6 hours. It is thought that the effect of SF, which is predominant in the swelling of CAG beads without BD, was hindered by the entanglement of BD. It appeared that the SF concentration has an effect on the BD release; the higher the SF concentration, the higher amount of BD released from the CAG beads. The release from this system basically follows Fick's law (Higuchi's expression). The increase in SF concentration decreased the Higuchi release coefficient. It was observed that the effect of small molecule is quite obvious, since the difference in Higuchi release coefficients of the CAG beads soaked in 1000-'g SF is less than non-soaked beads, about 25%.