Purified mast cells (MC), isolated from the rat peritoneum, were stimulated in vitro with recombinant human IFN-α 2a (rhIFN-α 2a) and studied ultrastructurally. Quantitative determination of histamine release was also performed. The following ultrastructural features were observed: (1) dilation of single granules, leading to the formation of cytoplasmic cavities filled with dissolved or eroded matrices; (2) induction of partially empty, non-fused granule containers close to unaltered resting granules, a process very suggestive of piecemeal degranulation; (3) focal exocytosis, characterized by opening of single granules to the cell exterior and/or fusion of a few granules into small secretory channels. Histamine release was slightly increased in rhIFN-α 2a-treated MC, although not to significant levels. These results indicate that rhIFN-α 2a induces a characteristic pattern of degranulation in rat peritoneal MC and that a small proportion of rhIFN-α 2a-stimulated MC shows ultrastructural features suggestive for piecemeal degranulation.