The possible role of mast cells in the initiation of inflammation was studied in genetically mast cell-deficient mice, WBB6F1-W/Wv. Inflammation was induced by i.p. injection of thioglycollate. The influx of neutrophils was markedly delayed in WBB6F1-W/Wv mice as compared to the WBB6F1-+/+, mice (congeneic controls). At the time (14 h) of maximum influx of neutrophils in WBB6F1-+/+ mice, thioglycollate caused a 3-fold increase in the total cell number in the peritoneal lavage fluid, and the neutrophil count was elevated 14-fold. At the same time point in W/Wv mice, the total cell number in the peritoneal lavage fluid was not increased significantly and the neutrophils were increased only three- to four-fold. Not only was the neutrophil influx in WBB6F1-W/Wv mice delayed, but the length of time during which the neutrophil count was elevated in the peritoneal fluid was significantly shortened. Transfer (i.p.) of mast cells cultured from the bone marrow of congeneic controls corrected the delay in the neutrophil influx. The magnitude of the neutrophil influx in WBB6F1-W/Wv mice was equivalent to that of congeneic controls 9 days after mast cell repletion. Histologic studies were performed to follow the migration and differentiation of mast cells after adoptive transfer into WBB6F1-W/Wv mice. No connective tissue mast cells could be identified on day 9 when the inflammatory reaction was restored. Migration of mast cells into the tissue, as studied in the cecum, progressed steadily. On day 9 after adoptive transfer, the mast cell number was 38% of congeneic controls. Therefore, the increase in thioglycollate-induced neutrophil influx in WBB6F1W/Wv mice after mast cell repletion seemed to be correlated, at least to some extent, with the migration of mast cells into tissues and not with differentiation into connective tissue mast cells. However, a certain maturation and differentiation may have occurred. These results suggest that mast cells play an important role, although they do not seem to be the only cell type responsible for the initiation of inflammation.