Compelling evidence indicates that exposure to urban airborne particulate matter (PM) affects health. However, how PM components interact with PM-size to cause adverse health effects needs elucidation, especially when considering soil and anthropogenic sources. We studied PM from Mexicali, Mexico, where soil particles contribute importantly to air pollution, expecting to differentiate in vitro effects related to PM-size and composition. PM samples with mean aerodynamic diameters ²2.5_m (PM 2.5) and ²10_m (PM 10) were collected in Mexicali (October 2005-March 2006) from a semi-urban (expected larger participation of soil sources) and an urban (predominately combustion sources) site. Samples were pooled by site and size, analyzed for elemental composition (particle-induced X-ray emission) and tested in vitro for: induction of human erythrocytes membrane disruption (hemolysis) (colorimetrically); inhibition of cell proliferation (ICP) (crystal violet) and TNF_/IL-6 secretion (ELISA) using J774.A1 murine monocytic cells; and DNA degradation using Balb/c3T3 cell naked DNA (electrophoretically). Results of PM elemental composition principal component analysis were used in associating cellular effects. Sixteen elements identified in PM grouped in two principal components: Component 1 (C 1): Mg, Al, Si, P, Cl, K, Ca, Ti, V, Cr, Fe, and Component 2 (C 2): Cu, Zn. Hemolysis was predominately induced by semi-urban-PM 10 (p<0.05) and was associated with urban-PM 10 C 1 (rEuro Surveillance (Bulletin Europeen Sur Les Maladies Transmissibles; European Communicable Disease Bulletin)0.62, pEuro Surveillance (Bulletin Europeen Sur Les Maladies Transmissibles; European Communicable Disease Bulletin)0.003). Major ICP resulted with semi-urban PM 2.5 (p<0.05). TNF_ was mainly induced by urban samples regardless of size (p<0.05) and associated with urban-PM 2.5 C 2 (rEuro Surveillance (Bulletin Europeen Sur Les Maladies Transmissibles; European Communicable Disease Bulletin)0.48, pEuro Surveillance (Bulletin Europeen Sur Les Maladies Transmissibles; European Communicable Disease Bulletin)0.02). Both PM 10 samples induced highest DNA degradation (p<0.05), regardless of location. We conclude that PM-size and PM-related soil or anthropogenic elements trigger specific biological-response patterns. © 2010 Elsevier Ltd.