Azelastine, an orally effective anti-allergic agent, has been demonstrated to inhibit the release of histamine and leukotrienes. This suggests that azelastine might alter the mobilization of intracellular Ca2+. We have examined the effect of azelastine on the change in intracellular free calcium concentration ([Ca2+])i) in guinea pig peritoneal macrophages induced by platelet activating factor (PAF-acether) or N-formylmethionyl-leucyl-phenylalanine (FMLP) using a fluorescent Ca2+ indicator, fura2. PAF-acether raised [Ca2+]i from 89 +/- 4 to 243 +/- 26 nM (n = 15) within 20 s after addition of PAF-acether in the presence of 2 mM EGTA. This indicates that the stimulation of macrophages by PAF-acether induced intracellular mobilization of Ca2+, and pretreatment with azelastine reduced the PAF-acether-induced increase in [Ca2+]i in a dose-dependent manner (IC50 = 16 microM). Azelastine also inhibited the FMLP-induced increase in [Ca2+]i. Furthermore, PAF-acether and FMLP both caused the release of prostaglandin E2 from macrophages, and pretreatment with azelastine reduced the PGE2 release dose dependently (IC50 = 10 microM). These results suggest that azelastine inhibits the release of Ca2+ from intracellular storage sites induced by PAF-acether or FMLP, and that this effect possibly causes reduction in the release of PGE2 from the cells.