Among the factors contributing to the overall uncertainty in the indirect effect of aerosols on climate is the still inadequately understood relationship between particle size, composition, and critical supersaturation. We employed two complementary approaches during the MILAGRO campaign to examine this relationship for the Mexico City aerosol. The dependence of critical supersaturation on particle size and hygroscopicity was quantified by using a differential mobility analyzer / tandem differential mobility analyzer (DMA / TDMA) upstream of a condensation nuclei counter and a cloud condensation nuclei counter, and downstream of the differential critical supersaturation separator (DScS), which separates from an introduced aerosol only those particles within a narrow critical supersaturation range. Additional details were obtained when the DScS was coupled with instruments capable of characterizing the CCN composition.