Ozone is known to produce an acute influx of neutrophils and alveolar epithelial cells secrete chemokines and can modulate inflammatory processes. However, direct exposure of alveolar epithelial cells and macrophages to ozone (O₃) produces little chemokine response. To determine if cell-cell interactions might be responsible, we investigated the effect of alveolar macrophage conditioned media after ozone exposure (MO₃CM) on alveolar epithelial cell chemokine production. Serum-free media was conditioned by exposing a rat alveolar macrophage cell line NR8383 to ozone for 1 h. Ozone stimulated secretion of IL-1, IL-1, and IL-18 from NR8383 cells, but there was no secretion of chemokines or TNF. Freshly isolated type II cells were cultured, so as to express the biological markers of type I cells, and these cells are referred to as type I-like cells. Type I-like cells were exposed to diluted MO₃CM for 24 h, and this conditioned medium stimulated secretion of CINC-1 (CXCL1) and MCP-1 (CCL2). Secretion of these chemokines was inhibited by the IL-1 receptor antagonist (IL-1Ra). Although both recombinant IL-1 and IL-1 stimulated alveolar epithelial cells to secrete chemokines, but recombinant IL-1 was 100 fold more potent than IL-1. Furthermore, neutralizing anti-rat IL-1 antibodies inhibited the secretion of chemokines by alveolar epithelial cells, whereas neutralizing anti-rat IL-1 antibodies had no effect. These observations indicate that secretion of IL-1 from macrophages stimulates alveolar epithelial cells to secrete chemokines that can elicit an inflammatory response.