A new functional magnetic resonance imaging (fMRI) technique for simultaneous detection (SIDE) of changes in perfusion and blood oxygenation level dependent (BOLD) contrast is described. Perfusion contrast is generated by using magnetically labeled endogenous water proton spins as a freely diffusible tracer. A single slice-selective inversion pulse is combined with dual echo echo-planar imaging to generate a spin-echo (SE) image sensitive to changes in perfusion and a gradient-echo (GE) image sensitive to changes in both perfusion and BOLD contrast. The SIDE technique was applied to detect functional changes induced by a visual search task. A theoretical analysis is provided to calculate quantitative maps of changes in cerebral blood flow (Delta CBF) and effective transverse relaxation time (Delta T-2*) from the corresponding signal changes in the SE and GE images. Since SE an GE images are generated from the same longitudinal magnetization, no errors due to spatial or temporal mismatch can arise in the quantification of Delta CBF and Delta T-2*. Copyright (C) 2000 John Wiley & Sons, Ltd.