Single crystals of B-DNA and Z-DNA oligomers were analyzed under high hydrostatic pressure and their behavior was compared to the A-DNA crystals already known. The amplitude of the base compression, when compared to the A-form of DNA (0.13 Å/GPa), was higher for the Z-DNA (0.32 Å/GPa) and was the highest for the B-DNA (0.42 Å/GPa). The B-DNA crystal degraded rapidly around 400–500 MPa, while the Z-structure was more resistant, up to 1.2 GPa.