Rabbit antisera against highly purified L-asparaginase from Serratia marcescens and from Escherichia coli showed up to 60% inhibition of the catalytic amidohydrolysis of L-asparagine when combined with the homologous enzyme. This inhibition was diminished somewhat against the heterologous enzyme. Kinetic studies in the presence of these antisera showed an increased Kmapp for both homologous and heterologous enzymes using L-asparagine as substrate. In contrast, kinetic studies employing the poor substrate, L-glutamine, showed activation attributable to specific antibodies. This was seen in lower Kmapp values and up to twofold increases in the Vmax over the normal rabbit serum controls. The high degree of cross-inhibition (approximately 80%) and the low degree of cross-reactivity in the quantitative precipitin test (approximately 34%) suggest that these two enzymes possess structural similarities located mainly in the regions of the catalytic sites.