Patterns of change in calcareous nannofossil assemblages during nannozones NP11 to NP16 on the southern Levant margin of the Tethys were observed from sections of early and middle Eocene age sediments of the Avedat Plateau, central Israel. A cooling process following the Early Eocene Climate Optimum (EECO) is supported by several events of biotic change over a 4 Ma interval. The rate of pelagic sedimentation varied from 7.5 at the EECO to 23.6 m Ma–1 at the cooling transition phase. Reduced numbers of discoasters mark the end of the oligotrophic regime within the NP13 nannozone, followed by an increase in nannofossil richness especially marked by Blackites and Chiasmolithus spp. In the middle part of the cooling process a prominent peak of reworked Paleocene taxa, up to 7% of total taxa, suggests that enhanced current activity caused re-sedimentation on the Levant margin slopes. When stability resumed in the upper part of the NP15–16 interval, Coccolithus-type placoliths became rare and Reticulofenestra-type forms became dominant. Calcareous nannoplankton response to this gradual cooling became irreversible in the late Palaeogene, but the change was, however, diachronous across the Tethys.