Success in grafting depends on the identification of a compatible rootstock (RS) that promotes rapid formation of vascular connections between the RS and the scion, and rapid resumption of root and shoot growth. In this study, we used compatible and incompatible Cucurbita rootstocks, with a melon (Cucumis melo L. 'Arava') scion, to identify physiological and biochemical factors in the scion-RS interface that could be associated with graft compatibility. Anatomical characterisation of the grafting interface showed that the regeneration and differentiation of vascular elements was similar, at first, in both compatible and incompatible grafted seedlings although, in the latter, a protective layer was formed, but did not interfere with communication between the RS and the scion. Water uptake and sugar distribution between the plant canopy and the roots, measured 14 d after grafting (DAG) were not correlated with compatibility or incompatibility. At 24 DAG, both water uptake and root sugar concentrations decreased significantly in the incompatible RS, reflecting deterioration of the RS. At 24 DAG, part of the RS collapsed, but only in incompatible grafted seedlings. Histochemical staining revealed that superoxide, H20 2, peroxidase (POX) activity, and lignin deposits at the scion-rootstock interface were similar in both compatible and incompatible grafting combinations at 14 DAG; but, at 24 DAG, H2O2 and superoxide levels were higher in the incompatible grafted transplants. In addition, cell-wall POX and superoxide dismutase (SOD) activities were lower in the incompatible RS-scion interface at 14 and 24 DAG. These results suggest that a physical barrier is unlikely to be formed between the incompatible partners early after grafting, but that lower anti-oxidant enzyme activities and higher levels of reactive oxygen species (ROS) in the incompatible RS-scion interface may be responsible for degradation of the grafting zone.