This article focuses on air pollution in specific urban microenvironments and conditions characterized by high relative concentration levels and by possible risk to human health. For this reason, monitoring of particle number concentration (PNC) with a wide, size-resolved particle-size range, and CO (an indicator of combustion sources, e.g., traffic), was performed in a variety of microenvironments. Concentrations of ultrafine particles (UFPs), size-fractionated particulate matter (PM), and carbon monoxide (CO) were measured in the central area of Milan over three-week-long periods, one each during summer, autumn, and winter, with three monitoring sessions per day. Experimental data were collected continuously during each monitoring period along an established urban pathway. To assess the relevance of time and spatial factors affecting atmospheric concentrations of UFPs, PM, and CO data were collected while walking or moving by different private and public means of transport. Measurements were divided on the basis of different microenvironments (MEs), seasons, days of the week, and periods of the day. Data analysis shows statistically significant differences across MEs and monitoring periods. The highest measured median concentrations and data variability were observed for busy streets, walking or moving by motorized vehicle (CO, UFP) and in metro trains (PM); the lowest concentrations were observed in park areas and in indoor environments. The highest concentrations were measured during working day morning monitoring sessions. Regarding seasonal variation, UFP, PM, and CO showed different patterns: the highest median concentrations were observed in summer for CO, and in autumn and winter for the UFP and PM. Appreciable differences among all MEs and monitoring periods were observed: concentration patterns and variations appear related to typical sources of urban pollutants (traffic), proximity to sources, and time of day. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resource: a file containing Table VI: Tau b (Kendall) index for non-parametric correlation tau test.].