Karoo picrites are divided into a volumetrically dominant high Ti-Zr (HTZ) group and a less abundant low Ti-Zr (LTZ) group. Distinguished in this way, it is then possible to use the comparison of major element compositions with those of experimentally determined partial melts of mantle peridotites to constrain the depth of segregation for each magma type. This approach also identifies the nature of source and residual mantle materials from which such magma segregation may have occurred. The LTZ group show uniformly shallow pressures (ca. 13–15 kb) of magma segregation and the HTZ group show a range of pressures (10 kb to > 30 kb) of segregation. In the HTZ group a range of K2O, TiO2 and Zr contents is observed, with greater concentrations in picrites which have segregated at higher pressures (high-NaK# HTZ picrites) relative to a low-NaK# HTZ picrite group (NaK#=[Na/2O+K2O][Na2O+K2O+CaO]). If we measure the refractory character of a mantle source peridotite by its CaO and Al2O3 content then it is shown that the LTZ picrites have segregated from sources which are more refractory than MORB or OIB sources and which lack the strong K, Ti and Zr enrichments of HTZ sources. Mixing of at least two mantle components is required to fully explain the major element and isotopic data in the HTZ group and is combined with variations in composition produced by different depths of magma segregation. Consideration of the major element phase relations coupled with trace element abundances and isotope data leads us to suggest that one component is the Kaapvaal lithospheric mantle (incompatible element enriched but relatively refractory with respect to basaltic components) and the other is asthenospheric mantle. This lithospheric mantle component is most evident in the high-NaK# HTZ picrite end-member which has segregated at a greater depth (ca. 18–32 kb). The asthenospheric component is most closely represented by the low-NaK# HTZ picrites which have segregated at pressures of 10–22 kb. The LTZ source, more refractory mantle than MORB, is inferred to be the shallow sub-continental lithospheric mantle which may also be the source of the low-MgO tholeiites related to these picrites, and therefore the source for the main phase of Karoo basaltic eruptions.