At least 9 and possibly as many as 12 extinction events of global or near-global impact can be discriminated in the mid-Palaeozoic (earliest Silurian to Early Carboniferous) on the basis of brachiopod, coral, conodont and ammonoid data, and the history of carbonate build-ups. Isotopic data from whole-rock samples are presented for three of these events, based on Australian carbonate sequences constrained by conodont data. These data represent the initial phase of a more extensive investigation using C, O, S, Sr and Nd isotopic signatures derived from conodonts, articulate and inarticulate brachiopod shell, and fish remains from numerous Australian and European sequences. The aim of the project is to identify isotopic responses to extinction events, and address causes for these changes. In limestone sections analysed so far, variations in carbon isotope compositions on a whole-rock scale are most marked at horizons that can be correlated with times of significant reduction in biomass and diversity. This is despite the fact that the whole rocks are in fact multicomponent systems with respect to carbon, in part arising from diagenetic rearrangements of carbon distribution within the scale of the whole rock. Thus, the carbon isotope data do provide evidence on a whole-rock scale for fundamental changes in the global carbon cycle that are correlative with extinction events. It is, however, unlikely that the magnitude of the isotopic shift will be precisely documented from such whole-rock analyses. The oxygen isotope results are less obviously related to the times of carbon isotope excursion; this contrast in apparent resilience to post-depositional modification of pristine isotope compositions exemplifies the extreme caution needed in evaluating isotopic data from carbonates.