Levels of urban pollution can be influenced largely by meteorological conditions and the topography of the area. The impact of the relative humidity (RH) on the daily average PM_2.5 concentrations was studied at several sites in a mid-size South American city at a high elevation over the period of nine years. In this work, we show that there is a positive correlation between daily average urban PM_2.5 concentrations and the RH in traffic-busy central areas, and a negative correlation in the outskirts of the city in more industrial areas. While in the traffic sites strong events of precipitation (≥9 mm) played a major role in PM_2.5 pollution removal, in the city outskirts, the PM_2.5 concentrations decreased with increasing RH independently of rain accumulation. Increasing PM_2.5 concentrations are to be expected in any highly motorized city where there is high RH and a lack of strong precipitation, especially in rapidly growing and developing countries with high motorization due to poor fuel quality. Finally, two models, based on a logistic regression algorithm, are proposed to describe the effect of rain and RH on PM_2.5, when the source of pollution is traffic-based vs. industry-based.