Primaquine, an 8-aminoquinoline, forms a cross-linked gel with periodate-oxidized gum arabic rapidly by simply mixing the drug with the oxidized polysaccharide due to Schiff's base formation between the two amino groups of primaquine and the aldehyde groups in the oxidized polysaccharide. The speed of gelation is determined by the degree of oxidation of polysaccharide, its quantity, and the drug payload. Estimation of the cross-linking density of the gels showed that the higher is the degree of oxidation of gum arabic, the higher is the cross-linking density. In vitro release of primaquine into phosphate buffered saline (PBS) at 37 degrees C demonstrated that the extent of release depended on the cross-linking density and drug payload. Repeated extraction using PBS soon after gel formation showed that not all of the primaquine was conjugated to the polysaccharide and the release seen in vitro was mostly from the unconjugated drug especially from matrices with higher cross-linking density. The gels were found to degrade in PBS, the kinetics of degradation being dependent on the cross-linking density. Cytotoxicity evaluation using MTT assay against L-929 mouse fibroblasts showed that oxidized gum arabic having a degree of oxidation of 50% was only very mildly cytotoxic at a concentration of 0.025 g/mL. An injectable, biodegradable drug depot with controlled release of primaquine over several days or weeks would be advantageous for long-term delivery of this drug against malaria or leishmaniasis, and the present study shows that a primaquine-polymer conjugate that can be formed in situ could be an interesting possibility.