Synoptic weather and ambient air quality synergistically influence human health. We report the relative risk of mortality from all non-accidental, respiratory-, and cardiovascular-related causes, associated with exposure to four air pollutants, by weather type and season, in 10 major Canadian cities for 1981 through 1999. We conducted this multi-city time-series study using Poisson generalized linear models stratified by season and each of six distinctive synoptic weather types. Statistically significant relationships of mortality due to short-term exposure to carbon monoxide, nitrogen dioxide, sulphur dioxide, and ozone were found, with significant modifications of risk by weather type, season, and mortality cause. In total, 61% of the respiratory-related mortality relative risk estimates were significantly higher than for cardiovascular-related mortality. The combined effect of weather and air pollution is greatest when tropical-type weather is present in the spring or summer.