Insufficient information has been available on measured ventilation rates and symptoms in office workers. Using U.S. EPA data from 100 large U.S. office buildings, we assessed relationships in multivariate models between ventilation/person and lower respiratory and mucous membrane symptoms. Three preliminary ventilation estimates were used, based on CO2 ratio in airstreams, peak indoor CO2 concentrations, and volumetric estimates of flow rates. Ventilation rates (VRs) from 6-17 cfm/person above the current 20 cfm/person guideline for offices were associated generally with reduced symptom prevalence, but further benefits were not evident from higher VRs. For all ventilation estimates, higher occupant density was independently associated with more symptoms. Findings suggest that VRs somewhat above current guidelines would reduce symptoms in office workers, and that occupant density may play an unrecognized role in ventilation requirements. Different findings for the various ventilation estimates were surprising. Clarification of these relationships, and validation of VR measurement methods are necessary.