Alveolar macrophages (AM) play a pivotal role in host lung defense mechanisms. Respiratory syncytial virus (RSV) stimulates secretion of proinflammatory cytokines in AM while it suppresses the cell's phagocytic ability. However, exposure of AM to ambient particulate matter (PM10) has been reported to inhibit RSV uptake. The mechanisms involved in the interaction between RSV and PM10 in AM are not known. We hypothesize that the cellular response of AM to RSV and PM10 is dependent on the sequence in which AM are exposed to these agents. In this study, we compared the sequential effect of RSV and PM10 exposure in vitro on the phagocytic function of guinea pig AM, the RSV Yield in AM, and the production of proinflammatory cytokines (interleukin [IL]-6, IL-8, and tumor necrosis factor [TNF]-alpha). The ability of AM to phagocytose PM10 was not affected by sequential exposure to RSV and PM10. RSV Yield was severely decreased in PM10-exposed AM, regardless of sequence of exposure, compared with AM that were not exposed to PM10 (P < 0.004). Exposure of AM to RSV and/or PM10 resulted in enhanced secretion of bioactive TNF-alpha compared with controls (P < 0.02), without synergistic or inhibitory interaction of these agents on TNF-alpha production. By contrast, exposure of AM to PM10 significantly decreased the production of RSV-induced IL-6 (P < 4 x 10(-6)) and IL-8 (P < 0.003). In summary, our findings suggest that PM10 exposure may interfere with mechanisms of RSV replication and viral-induced cytokine production in guinea pig AM, independent of the sequence of exposure to these agents.