Air change rates (ACRs) and interzonal flows are key determinants of indoor air quality (IAQ) and building energy use. This paper characterizes ACRs and interzonal flows in 126 houses, and evaluates effects of these parameters on IAQ. ACRs measured using weeklong tracer measurements in several seasons averaged 0.73 ± 0.76 h−1 (median = 0.57 h−1, n = 263) in the general living area, and much higher, 1.66 ± 1.50 h−1 (median = 1.23 h−1, n = 253) in bedrooms. Living area ACRs were highest in winter and lowest in spring; bedroom ACRs were highest in summer and lowest in spring. Bedrooms received an average of 55 ± 18% of air from elsewhere in the house; the living area received only 26 ± 20% from the bedroom. Interzonal flows did not depend on season, indoor smoking or the presence of air conditioners. A two-zone IAQ model calibrated for the field study showed large differences in pollutant levels between the living area and bedroom, and the key parameters affecting IAQ were emission rates, emission source locations, air filter use, ACRs, interzonal flows, outdoor concentrations, and PM penetration factors. The single-zone models that are commonly used for residences have substantial limitations and may inadequately represent pollutant concentrations and exposures in bedrooms and potentially other environments other where people spend a substantial fraction of time.