Abstract I present the results of a crustal rheological analysis of the Potenza 1990 and Molise 2002 (southern Italy) deep foci (10–25 km) strike–slip earthquake sequences ( M max =5.7) located in the upper half of the middle crust. The analysis consists of geotherms and two-mechanism (brittle frictional v. ductile plastic flow) strength envelopes. Strength envelopes are calculated along a sub-vertical E–W-striking inherited crustal-scale fault zone reactivated under a strike–slip tectonic regime. The effects of high pore-fluid pressure ( Pf ) and strain rate increase due to afterslip processes during the co-seismic and early post-seismic phases are evaluated. The results are compared with the depth-distribution of seismicity. Under long-term strain rates, the rheology predicts a brittle layer in the upper part of the middle crust embedded by two plastic horizons: the base of the carbonates and the Verrucano layer (above) and the lower part of middle crust (below). The best rheological model for the observed seismicity is that considering high Pf in the middle crust (λ≥0.65). Brittle faulting aided by high Pf in the middle crust is in agreement with the focal depths and magnitudes of the main shocks. The upward and downward widening of the brittle layer in the middle crust, due to the increased strain rate in the co-seismic and early post-seismic phases (afterslip), agrees with the width of the aftershock zones. The weak ductile layer at the base of the carbonates (and possibly within the Verrucano) appears to have an important role in delimiting the seismogenic faulting upwards and probably played a role in defining a seal to fluid up-flow along the fault zone.