We present hygroscopic and cloud condensation nuclei (CCN) relevant properties of the water-soluble fraction of Mexico City aerosol collected upon filters during the 2006 Megacity Initiative: Local and Global Research Observations (MILAGRO) campaign. Application of κ-Köhler theory to the observed CCN activity gave a fairly constant hygroscopicity parameter (κ = 0.28 ± 0.06) regardless of location and organic fraction. Köhler theory analysis was used to understand this invariance by separating the molar volume and surfactant contributions to the CCN activity. Organics were found to depress surface tension (10–15%) from that of pure water. Daytime samples exhibited lower molar mass (∼200 amu) and surface tension depression than nighttime samples (∼400 amu); this is consistent with fresh hygroscopic secondary organic aerosol (SOA) condensing onto particles during peak photochemical hours, subsequently aging during nighttime periods of high relative humidity. Changes in surface tension partially compensate for shifts in average molar volume to give the constant hygroscopicity observed, which implies the amount (volume fraction) of soluble material in the parent aerosol is the key composition parameter required for CCN predictions. This finding, if applicable elsewhere, may explain why CCN predictions are often found to be insensitive to assumptions of chemical composition and provides a very simple way to parameterize organic hygroscopicity in atmospheric models (i.e., κorg = 0.28ɛWSOC). Special care should be given, however, to surface tension depression from organic surfactants, as its nonlinear dependence with organic fraction may introduce biases in observed (and predicted) hygroscopicity. Finally, threshold droplet growth analysis suggests the water-soluble organics do not affect activation kinetics.