Exocytosis was studied in single rat peritoneal mast cells. Granule fusion was monitored by time-resolved capacitance measurements using the patch-clamp technique. Intracellular stimulation of mast cells with 20 μM GTP-γ-S stimulates exocytosis with a calcium-dependent time course. Secretion in response to receptormediated stimulation with compound 48/80 was completely abolished by treatment with pertussis toxin (IAP) at 180 ng/ml for 4 h. The time course of exocytosis in response to GTP-γ-S remained unaffected in IAP-treated cells supporting the involvement of a second GTP-binding protein in stimulus-secretion coupling.