NMDA receptor- (NMDAR) dependent long-term potentiation (LTP) has been extensively documented in hippocampal pyramidal neurons, where it requires autophosphorylation of the alpha isoform of Ca²⁺-calmodulin-dependent kinase type IIα (αCaMKII). We have recently shown that excitatory synapses onto a subset of inhibitory interneurons in stratum radiatum of the rat hippocampus also show Hebbian NMDAR-dependent LTP. αCaMKII has been reported to be absent from interneurons. We have therefore explored the role of CaMKII in Hebbian LTP in interneurons. We have used knock-in mutants to study the requirement of αCaMKII autophosphorylation. These mutants have the T286A point mutation in the endogenous αCaMKII gene preventing autophosphorylation. We performed gramicidin perforated patch recordings from stratum radiatum interneurons in hippocampal slices obtained either from αCaMKII-T286A mutant mice or from wild type mice. In mutant mice high-frequency stimulation (100 Hz, 1 s, x 2) of Schaffer collaterals resulted in LTP (90 ± 33% pathway-specific potentiation of EPSP initial slope; mean ± SD) lasting > 30 min in 7 interneurons, and failed to evoke LTP in 5 other cells. These results were not significantly different from either wild-type mice (LTP in 4 out of 7 cells; chi square test) or rats (LTP in 5 out of 9 cells). We verified that strong hyperpolarisation during the high-frequency stimulus prevented LTP induction in mutant mice (n = 4). These results argue against an obligatory role for αCaMKII. However, KN-62 (10 µM), a selective inhibitor of several CaMK isoforms, blocked LTP in the interneurons of αCaMKII-T286A mutant mice (n = 3). Hebbian LTP in stratum radiatum interneurons thus requires another KN-62-sensitive kinase such as βCaMKII. αCaMKII-independent Hebbian plasticity in interneurons may contribute to some residual memory formation observed in the αCaMKII-T286A mutant mice.